A Low-intensity Rim on T2-weighted Brainstem Imaging is a Normal Finding and a Mimicker of Superficial Siderosis

A Low-intensity Rim on T2-weighted Brainstem Imaging is a Normal Finding and a Mimicker of Superficial Siderosis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A Low-intensity Rim on T2-weighted Brainstem Imaging is a Normal Finding and a Mimicker of Superficial Siderosis Ryo Yamakuni, Hironobu Ishikawa, Shiro Ishii, Ryo Hiruta, Shoki Yamada, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5695756/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: In healthy participants, T2 superficial localized low intensity (T2-SLL) similar to superficial siderosis has been observed in the brainstem. This study aimed to determine the incidence and causes of T2-SLL. Methods: To determine the incidence, T2-weighted imaging (T2WI) was performed on 114 patients (68 males; mean age: 59.1 years) using a 3.0-T magnetic resonance (MR) scanner and visually assessed by two radiologists. T2-SLL presence in 22 brain areas was evaluated using the following system: 0 for absence, 1 for <50% surface, 2 for ≥50% but not the entirety, and 3 for the entirety. After assessing inter-rater agreement, the scores were averaged. To investigate the causes of T2-SLL, an experimental MR imaging (MRI) was performed on a healthy male volunteer. To evaluate the chemical shift effect, the bandwidth and encoding direction were modified. To assess the magnetic susceptibility effect, T2*WI was performed using varying echo times (TEs). Results: A moderate inter-rater score agreement (κ=0.556) was observed. T2-SLL was identified in all participants and was most frequently observed on the frontal and lateral sides of the midbrain and pons, with the highest occurrence on the frontal of the upper pons (median 2.0; interquartile range 2.0–3.0). In the experimental MRI, no differences in T2-SLL were observed across the varying bandwidths and encoding directions. However, the superficial low signal for T2WI thickened as the TE lengthened, similar to blood vessels, suggesting a magnetic susceptibility effect. Conclusion: T2-SLL can be regarded as a normal structure that may be associated with blood vessels. Nuclear Medicine & Medical Imaging superficial siderosis brain stem pons magnetic susceptibility effect partial volume effect chemical shift effect Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 INTRODUCTION Superficial siderosis (SS) is characterized by linear hemosiderin deposits in the subpial layer of the central nervous system, resulting from chronic bleeding into the subarachnoid space [ 1 – 3 ]. SS can be divided into infra- and supratentorial subtypes [ 4 , 5 ]. Supratentorial SS is primarily caused by cerebral amyloid angiopathy, whereas infratentorial SS is primarily caused by spinal dural abnormalities and cerebrospinal fluid (CSF) leakage [ 6 , 7 ]. Infratentorial SS is most commonly identified on magnetic resonance imaging (MRI), with a rim of low intensity in the brainstem, cerebellum, and spinal cord observed on T2-weighted imaging (T2WI), T2*WI, and susceptibility-weighted imaging [ 5 , 6 ]. Infratentorial SS presents with nonspecific symptoms and can progress if left untreated [ 8 ]. Therefore, an early MRI-based diagnosis is imperative. At our institution, we have commonly observed a rim of superficial low intensity, mainly localized to the midbrain and pons, on screening T2WI of asymptomatic patients and in all age groups, including children, adults, and older adults (Fig. 1 A), as well as on T2WI of symptomatic SS patients (Fig. 1 B). Thus, this localized rim of low intensity may be a normal phenomenon and not evidence of infratentorial SS. We refer to this phenomenon as T2 superficial localized low intensity (T2-SLL). To date, no studies have examined T2-SLL; therefore, the present study aimed to be the first to determine the incidence and causes of T2-SLL. MATERIALS AND METHODS Study Design This study combined a retrospective observational study component and a single-case experimental study component. The study protocol was approved by the appropriate institutional ethics committee (file numbers: REC2024-071 and REC2024-072). For the retrospective study component, the requirement for written informed consent was waived due to data anonymization and the retrospective study design. Written informed consent was obtained from the volunteer for the single-case experimental study component. This study was conducted in accordance with the ethical standards of the institutional and/or national research committee and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Retrospective Study Component Participants The patient selection flowchart for this study is shown in Fig. 2. Patients who had undergone brain MRI examinations, including whole-brain axial spin-echo T2WI using a 3.0-T MR scanner (MAGNETOM VIDA; Siemens Healthineers, Erlangen, Germany) at our institution between June 2024 and July 2024 were selected from the database. Since brain MRIs of neonates and infants differ from those of older age groups [ 9 ], participants had to be at least 1 year of age at the time of the MRI examination to be considered eligible for inclusion. MRI scans with artifacts, including metal or motion, were excluded. Additionally, participants with lesions in any of the 22 evaluated brain areas were excluded. MRI Whole-brain axial spin-echo T2WI was acquired using clinical imaging sequences. The axial plane extended from the anterior commissure to the orbitomeatal line (OM) line. Representative T2WI parameters are listed in Table 1 . Table 1 Representative parameters of axial spin echo T2WI in clinical use at our institution MR Scanner MAGNETOM VIDA Vender Siemens Healthineers Magnetic field 3.0-Tesla TR 4500 TE 104 FA 160 Matrix 294*368 NEX 1 Slice thickness 5 mm Slice gap 1 mm Field of View 220 mm T2WI, T2 weighted image; TR, Repetition Time; TE, Echo Time; FA, Flip Angle; NEX, Number of Excitations; FOV, Field of View Imaging Analysis For the imaging analysis, T2-SLL was defined as a low signal intensity on the brain surface, similar to or lower than that of the substantia nigra (SN), which has physiological iron deposition [ 10 ] and mainly shows a low signal intensity on T2WI [ 11 ]. Iron deposition in the SN is completed earlier than in the globus pallidus, putamen, and caudate nucleus and is less affected by aging [ 12 ]. Therefore, the SN was used as a reference region to identify a low T2WI signal intensity. Visual estimation was performed independently by two radiologists (with 23 and 11 years of experience) who reviewed brain T2WI MRI scans using workstation software (EV Insite 4.2; PSP Corporation, Tokyo, Japan) to determine the presence of T2-SLL. To facilitate a comparison with the midbrain SN, reversed T2WI was also evaluated. The window level of the reversed T2WI was set near each participant’s SN signal value, and a narrow window width (approximately 150) was set. The presence of T2-SLL was evaluated at 22 locations within the following areas: lower midbrain, upper pons, lower pons, medulla oblongata, cerebellum, and temporal lobe. The locations in the midbrain, pons, and medulla oblongata were defined based on the cisterns and ventricles that encountered the brainstem. The cistern regions were defined based on a report by Morris et al.[ 13 ]. For the cerebellum, both the left and right cerebellar hemisphere surfaces were evaluated, and for the temporal lobe, the surfaces of the left and right temporal poles were assessed. Additional details of the evaluation sites are presented in Table 2 and Fig. 3 . Table 2 List of twenty-two areas to assess T2 superficial localized low intensity, and T2-SLL score of each areas No. Area Contact cistern or ventricle T2-SLL score A. Lower midbrain: inferior colliculus level median IQR 1 frontal surface interpeduncular cistern 2.0 1.0–2.0 2 right frontolateral surface right crural cistern 1.5 1.0–2.0 3 left frontolateral surface left crural cistern 1.5 1.0–2.0 4 right lateral surface right ambient cistern 2.0 2.0–2.0 5 left lateral surface left ambient cistern 2.0 2.0–2.0 6 posterior surface quadrigeminal cistern 0.5 0.0–1.0 B. Upper pons: superior cerebellar peduncle level median IQR 7 frontal surface prepontine cistern 2.0 2.0–3.0 8 right lateral surface right cerebellopontine angle cistern 2.0 1.5–2.4 9 left lateral surface left cerebellopontine angle cistern 2.0 2.0–2.0 10 posterior surface forth ventricle 1.0 0.5–1.0 C. Lower pons: middle cerebellar peduncle level median IQR 11 frontal surface prepontine cistern 1.0 1.0–2.0 12 right lateral surface right cerebellopontine angle cistern 1.5 1.0–2.0 13 left lateral surface left cerebellopontine angle cistern 1.5 1.0–2.0 14 posterior surface forth ventricle 1.0 1.0–1.5 D. Medulla oblongata: glossopharyngeal nerve root level median IQR 15 frontal surface premedullary cistern 1.5 1.0–2.0 16 right lateral surface right lateral cerebellomedullary cistern 1.0 0.5–1.0 17 left lateral surface right lateral cerebellomedullary cistern 1.0 0.5–1.0 18 posterior surface forth ventricle 0.5 0.0–1.0 E. Others location median IQR 19 right temporal lobe surface right temporal pole 0.0 0.0–0.0 20 left temporal lobe surface left temporal pole 0.0 0.0–0.0 21 right cerebellar hemisphere surface middle cerebellar peduncle level 0.0 0.0–0.0 22 left cerebellar hemisphere surface middle cerebellar peduncle level 0.0 0.0–0.0 IQR, interquartile range; T2-SLL was evaluated for each of the 22 areas using the following scoring system: 0 points for the absence of T2-SLL, 1 point for < 50% of the surface, 2 points for ≥ 50% of the surface but not the entire surface, and 3 points for the entire surface (Fig. 4 ). A scoring example is shown in Supplementary Fig. 1. After assessing inter-tester agreement, the analysts’ scores for each area were averaged. Then, each participant’s T2-SLL scores in the 22 areas were summed (summed T2-SLL score). Statistical Analysis Nonparametric statistical methods were employed because the Shapiro–Wilk test revealed a non-normal distribution of T2-SLL scores. Inter-tester agreement was assessed using weighted kappa statistics. The κ values were interpreted as follows: poor (κ = 0.0), small/slight (κ = 0.0–0.20), fair (κ = 0.21–0.40), moderate (κ = 0.41–0.60), substantial (κ = 0.61–0.80), and almost perfect (κ = 0.81–1.00) [ 14 ]. The Friedman test was performed to evaluate differences in the T2-SLL scores of the 22 areas, and the Scheffé’s post-hoc test was performed for multiple comparisons. To confirm age-dependent differences in summed T2-SLL scores, participants were categorized into three subgroups: children (under 18 years), adults (18 to under 65 years), and older adults (≥ 65 years). The summed T2-SLL scores of the subgroups were compared using the Kruskal-Wallis test, and the Scheffé’s post-hoc test was performed to specifically compare two groups. All statistical analyses were performed using a commercial software program (Bell Curve for Excel 4.07; Social Survey Research Information, Tokyo, Japan). Statistical significance was set at P < 0.05. Single-case Experimental Study Component Participant The participant was a 40-year-old, healthy male volunteer without a history of neurological diseases, including stroke, subarachnoid hemorrhage, cerebral hemorrhage, or head injury, and without neurological symptoms, including those suggestive of cerebrospinal fluid hypovolemia or SS, such as headaches [ 15 , 16 ], ataxia [ 17 ], or hearing loss [ 5 , 8 ]. MRI was performed to evaluate the effects of chemical shifts and magnetic susceptibility on T2-SLL. MRI Scanner Brain MRI was performed using a 3.0-T MR scanner (MAGNETOM VIDA; Siemens Healthineers) and a 64-channel head coil. Distribution of T2-SLL To investigate the distribution of T2-SLL, brainstem-focused, high-resolution T2WI was performed using the following sequences: axial T2WI; repetition time (TR)/echo time (TE), 6230/99 ms; flip angle, 147°; matrix, 288 × 288; field of view (FOV), 160 mm; slice thickness, 2 mm, frequency encoding, right-left (RL) direction; and bandwidth, 395 Hz/pix. Deep Resolve (Siemens Healthineers), a deep-learning reconstruction method, was applied to denoise and improve resolution. The distribution of T2-SLL was assessed in the same 22 areas used for the retrospective study component. Chemical Shift Effect First, axial T2WI (TR/ TE, 4500/104 ms; flip angle, 160°; matrix, 368 × 294; FOV, 220 mm; slice thickness, 5 mm; frequency encoding, RL direction; bandwidth, 400 Hz/pix) was performed as a standard. To avoid the influence of filters, images were created without applying filters except for the sensitivity correction filter, which corrects for contrast irregularities. To assess the effect of the chemical shift on T2-SLL, the bandwidths and encoding directions were altered from those of the standard T2WI. The bandwidth was adjusted to 200 and 100 Hz/pix to determine whether the T2-SLL varied in each image, while the other T2WI parameters remained unchanged. Second, the encoding direction was modified to left-right, anterior-posterior, and posterior-anterior, while the other T2WI parameters, including the bandwidth, were consistent with the standard T2WI. Magnetic Susceptibility Effect To determine whether T2-SLL exhibits the magnetic susceptibility effect, the TE of T2*WI was varied to determine whether any alterations in the size of the T2-SLL occurred [ 18 , 19 ]. First, axial and sagittal T2*WI (TR/TE, 1800/10 ms; flip angle, 20°; matrix, 224 × 224; FOV, 220 mm; slice thickness, 2 mm) was performed as a standard T2*WI. Subsequently, the TE was changed to 20, 30, 40, and 50 ms, while the other T2*WI parameters were unchanged. Partial Volume Effect (PVE) To assess the PVE on T2-SLL, the slice thickness was changed to 2, 5, and 10 mm, while the other parameters (TR/TE, 4500/103 ms; flip angle, 160°; matrix, 320 × 320; FOV, 160 mm; bandwidth, 400 Hz/pix) remained unchanged. Other MRI Sequences T1-weighted imaging (T1WI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), diffusion-weighted imaging (DWI), and time-of-flight magnetic resonance angiography (TOF MRA) were also performed to rule out neurological diseases, such as brain infarctions, subdural hematomas, or brain tumors. Comparison Between MRI Scanners To confirm that T2-SLL is not dependent on a specific MRI scanner, brain T2WI was performed using two additional 1.5-T MR scanners (Vantage Fortian; Canon Medical Systems, Otawara, Japan and Optima 450w; GE Healthcare, Milwaukee, WI, USA). Axial spin-echo T2-weighted brain images were acquired using clinical imaging sequences optimized for each MRI system, as routinely performed at our institution. The axial plane was aligned along the OM line. These T2WI parameters are listed in Supplementary Table 1. RESULTS Retrospective Study Component General Information about Enrolled Participants In this study, 126 patients met the inclusion criteria. However, per the exclusion criteria, patients with lesions in the 22 evaluation areas were excluded, including those with brain infarctions (n=2), brain tumor invasion (n=5), post-brain tumor resections (n=4), or large aneurysms (n=1). No participants were excluded due to motion or metal artifacts. Overall, the present study included 114 patients (68 males and 46 females; mean age: 59.1; range, 6–84 years), with eight children (three males, mean age: 13.4 years), 54 adults (32 males, mean age: 49.4 years), and 52 older adults (33 males, mean age: 76.1 years). Details about participants’ diagnoses are shown in Supplementary Table 2. Inter-tester Agreement Moderate inter-tester agreement for T2-SLL scoring existed between the two radiologists, with a κ=0.556 (95% confidence interval [CI] 0.527–0.586). A cross-tabulation table with the radiologists’ T2-SLL scores is shown in Supplementary Table 3.  Location and Incidence of T2-SLL T2-SLL was observed in all 114 participants, though its extent varied among individuals. Among the 22 areas, the median and interquartile range (IQR) of the T2-SLL score for the frontal surface of the upper pons was the highest (2.0; IQR 2.0–3.0). T2-SLL was also identified in a wide range of midbrain and upper pons areas other than the posterior surface of the lower midbrain (0.5; IQR 0.0–1.0) and upper pons (1.0; IQR 0.5–1.0). T2-SLL was identified less frequently on the surfaces of the temporal lobes and cerebellar hemispheres than in other areas (Table 2, Supplementary Figure 1). The Friedman test revealed a significant difference in T2-SLL scores according to area ( P < 0.001). Scheffé’s post-hoc test results are shown in Supplementary Table 2. Age-dependent Differences in the Frequency of T2-SLL The median summed T2-SLL score increased with age. The median for each age group was 24.3 (IQR 22.9–25.8) for children, 25.8 (IQR 23.5–27.0) for adults, and 26.0 (IQR 24.0–28.0) for older adults (Figure 5). However, the Kruskal-Wallis test revealed no significant differences in the summed T2-SLL scores according to age group ( P = 0.24). Single-case Experimental Study Component Distribution of T2-SLL T2-SLL was observed on the entire frontal surface of the upper pons and the left lateral surface of the lower pons on a high-resolution T2WI of the participant. T2-SLL was also observed extensively in the midbrain and pons but not on the surfaces of the temporal lobes or cerebellar hemispheres (Supplementary Figure 3). Chemical Shift Effect No differences in T2-SLL were observed between T2WI images with different bandwidths or encoding directions (Supplementary Figure 4). Therefore, T2-SLL was considered unrelated to the chemical shift. Magnetic Susceptibility Effect On standard T2*WI (TE = 10), T2-SLL was observed in the same areas as on T2WI, and these regions thickened as the TE lengthened (Figure 6). In addition, the vessels observed in the same slice enlarged as the TE lengthened. Therefore, T2-SLL was considered to exhibit the magnetic susceptibility effect. PVE T2-SLL became unclear when the slice thickness increased from 2 mm to 5 mm and 10 mm (Supplementary Figure 5). Other MRI Findings No neurological diseases were identified using other MRI sequences, including T2WI, T2*WI, T1WI, T2-FLAIR, DWI, or TOF MRA (data not presented). Comparison Between Different MRI Scanners No significant differences in T2-SLL were observed between T2WI performed using the three different MRI scanners (Supplementary Figure 6). DISCUSSION This combined retrospective observational and single-case experimental study investigated the frequency and causes of T2-SLL. Specifically, T2-SLL was commonly observed on the lateral and frontal sides of the midbrain and pons and was found to exhibit the magnetic susceptibility effect. No previous studies have been conducted on T2-SLL to date. However, a magnetic susceptibility map from a previous 7T-MRI study confirmed the magnetic susceptibility effect on the surface of the brainstem, similar to the experimental study results observed in the present study [20]. In the previous study, the magnetic susceptibility effect was clearly observed at the upper pons on the frontal and lateral surfaces and was attributed to a magnetization effect related to the fibers of the middle cerebellar peduncle. However, at the lower pons level, the middle cerebellar peduncle showed no high magnetic susceptibility. Moreover, in tensor imaging conducted simultaneously in the previous study, the fibers of the cerebellar peduncle were depicted; however, they were observed over a wider range than the range where the magnetic susceptibility effect was confirmed. The magnetic susceptibility effect was localized to the surface; therefore, it is unlikely that T2-SLL and surface magnetic susceptibility effects are associated with nerve fibers. When T2WI shows a low signal intensity, the following factors are potential causes: gadolinium, hemoglobin, hemosiderin, melanin, mucous, high cellular density, mineral substances (such as iron, copper, and calcium), flow voids due to blood or CSF flow, and air-containing spaces [21]. Hemoglobin, hemosiderin, melanin, minerals, and blood in the vessels exhibit the magnetic susceptibility effect [22]. In the present study, T2-SLL was observed across a wide range of age groups and in asymptomatic participants. Therefore, this phenomenon cannot be regarded as a lesion, and hemosiderin deposition (i.e., siderosis) is unlikely. In the brain, neuromelanin is present in the SN and locus coeruleus [23] but does not exhibit a superficial brainstem-spreading distribution. Therefore, T2-SLL may instead be related to blood vessels or mineral deposition. Although no significant differences were observed, the summed T2-SLL scores of children tended to be lower than those of adults or older adults in the present study. Therefore, the possibility that age-related mineral deposits are causing T2-SLL cannot be ruled out. Mineral deposition can be observed using Perls’ Prussian blue staining for iron [24], rhodanine staining for copper [25], and Von Kossa staining for calcium [26]. However, to date, physiological mineral deposition in the brainstem has not been reported. Numerous minute arteries and veins develop in the brainstem. For example, the pons has numerous arterial and venous networks that run along the surface of the brain and connect to the capillaries [27, 28]. These blood vessels may be observable as superficial low-intensity vessels exhibiting the magnetic susceptibility effect. In the present study, higher T2-SLL scores were observed on the frontal sides of the pons and midbrain. Conversely, the temporal lobe and cerebellar hemisphere surfaces exhibited lower T2-SLL scores. This discrepancy may be attributable to differences in the development of the associated blood vessels on the brain surface [29]. The frontal side of the brainstem is mainly composed of white matter, whereas the areas underlying the surfaces of the temporal lobes and cerebellar hemispheres are mainly composed of gray matter. Therefore, the structure of the capillaries on the surface may differ depending on whether the structure that exists directly below them is either white or gray matter. However, no study has specifically examined the degree of blood vessel development on the brain surface. Further anatomical and histological studies are required to confirm these findings. In the retrospective observational study component, there was a moderate inter-tester agreement for T2-SLL scoring. However, some cases showed larger discrepancies in T2-SLL scoring between the two radiologists, which may be related to the PVE and slice thickness [30]. The midbrain and pons are thicker regions in the cephalocaudal direction, and the center of the slice may not always align with the center of other key structures, such as the inferior colliculus or superior cerebellar peduncle, on a 5-mm-thick image. Therefore, for cases with large discrepancies in the two radiologists’ evaluations, it is possible that the cross-sections in which the evaluations were performed were different. Moreover, the brainstem region has a complex structure, and thick-slice images may obscure the limbus due to the PVE. The 5-mm-thick images were more prone to PVE, and a one-slice deviation could have led to large differences in the evaluations. Indeed, in the experimental study, T2-SLL was observed evenly and extensively around the ventral side of the pons on 2 mm-thickness, high-resolution T2WI. However, T2-SLL became more obscured as the slices became thicker. Therefore, further studies with thinner slices are required to confirm a more accurate normal distribution of T2-SLL. Although no significant differences were observed in the present study, the T2-SLL scores tended to be lower in children, which may be related to the PVE. Since children have smaller head sizes [31], PVE is more likely to occur when imaging is performed using the same FOV and voxel size parameters as in adults. In the single-case experimental study component, we observed uniform T2-SLL in the pons and midbrain using 2-mm imaging. In contrast, when the slice thickness was increased, T2-SLL became unclear. The PVE may, therefore, explain the tendency toward lower T2-SLL scores in children. The strength of the present study is that it was the first to focus on T2-SLL and to investigate its frequency and causes. However, it also had several limitations. First, both study components involved a single center. Second, contrast enhancement was not performed in the present study. At our institution, unenhanced T1WI is performed using a fast-spin echo sequence, whereas contrast-enhanced T1WI is routinely performed using a gradient echo sequence. To accurately determine the contrast effect, pre- and post-enhanced T1WI must be performed using the same sequence. Moreover, performing contrast-enhanced MRI in healthy volunteers is not recommended due to the risk of side effects. However, further studies, including contrast studies, are necessary to confirm that T2-SLL originates from small vessels. CONCLUSIONS This study demonstrated that a rim of a superficial low-intensity signal on T2WI can be observed in the midbrain and pons of healthy individuals and that these areas exhibit the magnetic susceptibility effect. T2-SLL can, therefore, be considered a normal structure, possibly associated with small surface blood vessels. When diagnosing SS using T2WI, it is important to consider the possibility of misidentifying T2-SLL as early-stage SS. Statements and Declarations Competing Interests: The authors declare no conflicts of interest related to the content of this article. Ethics approval: This study combined a retrospective observational study component and a single-case experimental study component. The study protocol was approved by the appropriate institutional ethics committee (file numbers REC2024-072 [retrospective observational study] and REC2024-071 [single-case experimental study]) and conducted in accordance with the ethical standards of the institutional and/or national research committee and the 1964 Helsinki Declaration and its later amendments, or comparable ethical standards. Consent to participate: For the retrospective study component, the requirement for written informed consent was waived due to data anonymization and the retrospective study design. Written informed consent was obtained from the volunteer for the single-case experimental study component. References Kumar N, Cohen-Gadol AA, Wright RA, et al (2006) Superficial siderosis. 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Biol Trace Elem Res 153:257–268. https://doi.org/10.1007/s12011-013-9665-0 Schneider MR (2021) Von Kossa and his staining technique. Histochem Cell Biol 156:523–526. https://doi.org/10.1007/s00418-021-02051-3 Naidich TP, Duvernoy HM, Delman BN, et al (2009) Vascularization of the Cerebellum and the Brain Stem. In: Duvernoy’s Atlas of the Human Brain Stem and Cerebellum. Springer, Vienna, pp 159–217 Takahashi S (2011) Intracranial Arterial System: Infratentorial Arteries. In: Neurovascular Imaging. Springer London, London, pp 131–188 Viviani R (2016) A Digital Atlas of Middle to Large Brain Vessels and Their Relation to Cortical and Subcortical Structures. Front Neuroanat 10:12. https://doi.org/10.3389/fnana.2016.00012 Tohka J, Zijdenbos A, Evans A (2004) Fast and robust parameter estimation for statistical partial volume models in brain MRI. Neuroimage 23:84–97. https://doi.org/10.1016/j.neuroimage.2004.05.007 Nellhaus G (1968) Head circumference from birth to eighteen years. Practical composite international and interracial graphs. Pediatrics 41:106–114. https://doi.org/10.1542/peds.41.1.106 Tables Table 1. Representative parameters of axial spin echo T2WI in clinical use at our institution MR Scanner MAGNETOM VIDA Vender Siemens Healthineers Magnetic field 3.0-Tesla TR 4500 TE 104 FA 160 Matrix 294*368 NEX 1 Slice thickness 5 mm Slice gap 1 mm Field of View 220 mm T2WI, T2 weighted image; TR, Repetition Time; TE, Echo Time; FA, Flip Angle; NEX, Number of Excitations; FOV, Field of View Table 2. List of twenty-two areas to assess T2 superficial localized low intensity, and T2-SLL score of each areas No. Area Contact cistern or ventricle T2-SLL score A. Lower midbrain: inferior colliculus level median IQR 1 frontal surface interpeduncular cistern 2.0 1.0 – 2.0 2 right frontolateral surface right crural cistern 1.5 1.0 – 2.0 3 left frontolateral surface left crural cistern 1.5 1.0 – 2.0 4 right lateral surface right ambient cistern 2.0 2.0 – 2.0 5 left lateral surface left ambient cistern 2.0 2.0 – 2.0 6 posterior surface quadrigeminal cistern 0.5 0.0 – 1.0 B. Upper pons: superior cerebellar peduncle level median IQR 7 frontal surface prepontine cistern 2.0 2.0 – 3.0 8 right lateral surface right cerebellopontine angle cistern 2.0 1.5 – 2.4 9 left lateral surface left cerebellopontine angle cistern 2.0 2.0 – 2.0 10 posterior surface forth ventricle 1.0 0.5 – 1.0 C. Lower pons: middle cerebellar peduncle level median IQR 11 frontal surface prepontine cistern 1.0 1.0 – 2.0 12 right lateral surface right cerebellopontine angle cistern 1.5 1.0 – 2.0 13 left lateral surface left cerebellopontine angle cistern 1.5 1.0 – 2.0 14 posterior surface forth ventricle 1.0 1.0 – 1.5 D. Medulla oblongata: glossopharyngeal nerve root level median IQR 15 frontal surface premedullary cistern 1.5 1.0 – 2.0 16 right lateral surface right lateral cerebellomedullary cistern 1.0 0.5 – 1.0 17 left lateral surface right lateral cerebellomedullary cistern 1.0 0.5 – 1.0 18 posterior surface forth ventricle 0.5 0.0 – 1.0 E. Others location median IQR 19 right temporal lobe surface right temporal pole 0.0 0.0 – 0.0 20 left temporal lobe surface left temporal pole 0.0 0.0 – 0.0 21 right cerebellar hemisphere surface middle cerebellar peduncle level 0.0 0.0 – 0.0 22 left cerebellar hemisphere surface middle cerebellar peduncle level 0.0 0.0 – 0.0 IQR, interquartile range; Additional Declarations The authors declare no competing interests. Supplementary Files PonsT2WIFigSupp1.pdf Supplementary Fig. 1 Example of T2-SLL scoring. (a) midbrain, (b) upper pons (at the superior cerebellar peduncle level), (c) lower pons (at the middle cerebellar peduncle level), (d) medulla oblongata, (e) cerebellum (at the middle cerebellar peduncle level), and the temporal lobe PonsT2WIFigSupp2.pdf Supplementary Fig. 2 Median and interquartile range of T2 superficial localized low intensity in 22 brain areas PonsT2WIFigSupp3.pdf Supplementary Fig. 3 T2-SLL distribution on high-resolution T2WI from the experimental MRI study component. (a) midbrain, (b) upper pons (at the superior cerebellar peduncle level), (c) lower pons (at the middle cerebellar peduncle level), (d) medulla oblongata, (e) cerebellum (at the middle cerebellar peduncle level), and the temporal lobe PonsT2WIFigSupp4.pdf Supplementary Fig. 4 Chemical shift effect of T2-SLL PonsT2WIFigSupp5.pdf Supplementary Fig. 5 Partial volume effect of T2-SLL. T2-SLL became unclear when the slice thickness was increased from 2 mm to 5 mm and 10 mm PonsT2WIFigSupp6.pdf Supplementary Fig. 6 Comparison of T2-SLL between three different MRI scanners. T2-SLL was observed on T2WI using all three scanners PonsT2WITableSupp1.pdf Supplementary Table 1. Parameters of three different MRI scnanner axial spin echo T2WI PonsT2WITableSupp2.pdf Supplementary Table 2. Details of the diagnosis of 114 participants PonsT2WITableSupp3.pdf Supplementary Table 3. Cross-tabulation table of T2-SLL scoreing between two radiologists PonsT2WITableSupp4.pdf Supplementary Table 4. Post-hoc Scheffe's paired comparison for T2-SLL score difference among twenty-two areas Cite Share Download PDF Status: Posted 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-5695756","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":401503040,"identity":"51b85610-6658-4699-9aa7-20f174dfb80e","order_by":0,"name":"Ryo Yamakuni","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1ElEQVRIiWNgGAWjYJACxgYGBh5+5gMIHnFaJNsSSNTCYHAsgUhHGRw/nfhxZtsdGeNj3GkSDDV2DMyzCVhjcCZ3s+TGtmc8Zsd4t0kwHEtmYJxzgICWA7kbJB+2HeYxu98L1MJ2gIFxBgEXGpx/u/knSItxG8iWf8RouZG7DeiwwzwGbEAtjG1EaJG88Xab5Yxzh3kkjvFutkjsS+Yh6Be+87mbb/aUHbbnb+PdeOPDNzs5Q0IhpoBiJNBJPIYz8OtgkMcwUl6CgJZRMApGwSgYcQAAlIFIVZTmrAAAAAAASUVORK5CYII=","orcid":"","institution":"Department of Radiology and Nuclear Medicine, Fukushima Medical University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Ryo","middleName":"","lastName":"Yamakuni","suffix":""},{"id":401503041,"identity":"099b59c5-2c6e-489d-ac58-d18dcb35aa47","order_by":1,"name":"Hironobu Ishikawa","email":"","orcid":"","institution":"Department of Radiology, Fukushima Medical University 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Medicine","correspondingAuthor":false,"prefix":"","firstName":"Shoki","middleName":"","lastName":"Yamada","suffix":""},{"id":401503045,"identity":"08f028aa-7d45-4728-a80d-36c46e5c7ee5","order_by":5,"name":"Shinya Seino","email":"","orcid":"","institution":"Department of Radiology, Fukushima Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shinya","middleName":"","lastName":"Seino","suffix":""},{"id":401503046,"identity":"6263543e-8433-44e0-942b-455f9c89b267","order_by":6,"name":"Takeyasu Kakamu","email":"","orcid":"","institution":"Department of Hygiene and Preventive Medicine, Fukushima Medical University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Takeyasu","middleName":"","lastName":"Kakamu","suffix":""},{"id":401503047,"identity":"283692c9-ebb6-4a2d-bab1-398c3806e5fb","order_by":7,"name":"Noriaki Tomura","email":"","orcid":"","institution":"Department of Radiology, Southern TOHOKU General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Noriaki","middleName":"","lastName":"Tomura","suffix":""},{"id":401503048,"identity":"593029dd-7703-4849-993d-1a1d3d262b6f","order_by":8,"name":"Kenji Fukushima","email":"","orcid":"","institution":"Department of Radiology and Nuclear Medicine, Fukushima Medical University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kenji","middleName":"","lastName":"Fukushima","suffix":""},{"id":401503049,"identity":"86880292-9dcd-459e-b8be-ed3bcac2d638","order_by":9,"name":"Hiroshi Ito","email":"","orcid":"","institution":"Department of Radiology and Nuclear Medicine, Fukushima Medical University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hiroshi","middleName":"","lastName":"Ito","suffix":""}],"badges":[],"createdAt":"2024-12-23 01:38:12","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-5695756/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5695756/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":73756741,"identity":"747fc019-f2eb-4eb7-a580-38c001ed0514","added_by":"auto","created_at":"2025-01-14 10:45:08","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":333252,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of T2 superficial localized low intensity and superficial siderosis\u003c/p\u003e\n\u003cp\u003e(a) Brain axial T2WI of a 70-year-old man reveals a capsular low-signal area on the ventral side of the pons and around the midbrain (indicated by arrows). In addition, other regions exhibit scattered low-signal areas on the surface. The patient did not present with any neurological symptoms, and an MRI was performed to screen for brain metastases.\u003c/p\u003e\n\u003cp\u003e(b) Brain axial T2WI of an 82-year-old man recently diagnosed with superficial siderosis shows a distinct low-signal area not only on the ventral side of the pons but also extending over a wide region\u003c/p\u003e","description":"","filename":"PonsT2WIFig11.png","url":"https://assets-eu.researchsquare.com/files/rs-5695756/v1/449e83bb7a4919cf4b54a6ba.png"},{"id":73756743,"identity":"3d17b6e8-213d-461a-81d6-49fd478ccd22","added_by":"auto","created_at":"2025-01-14 10:45:09","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":40799,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of patient selection\u003c/p\u003e","description":"","filename":"PonsT2WIFig21.png","url":"https://assets-eu.researchsquare.com/files/rs-5695756/v1/edddd0544c642bbf90407f2b.png"},{"id":73756745,"identity":"37402526-9140-4642-a047-df5c45934670","added_by":"auto","created_at":"2025-01-14 10:45:09","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":312209,"visible":true,"origin":"","legend":"\u003cp\u003eThe 22 areas used to assess for T2 superficial localized low intensity\u003c/p\u003e\n\u003cp\u003e(a) midbrain, (b) upper pons (at the superior cerebellar peduncle level), (c) lower pons (at the middle cerebellar peduncle level), (d) medulla oblongata, (e) cerebellum (at the middle cerebellar peduncle level), and the temporal lobe. The definition of each site is presented in Table 2\u003c/p\u003e","description":"","filename":"PonsT2WIFig3.png","url":"https://assets-eu.researchsquare.com/files/rs-5695756/v1/331d4920a64ebafeddca177b.png"},{"id":73756754,"identity":"3ca06c5d-37cf-4f6e-be7d-5b7d52cc0464","added_by":"auto","created_at":"2025-01-14 10:45:09","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":581314,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentative examples of the 0–3 scoring system for T2 superficial localized low intensity (T2-SLL)\u003c/p\u003e\n\u003cp\u003e(a) 0 points for the absence of T2-SLL, (b) 1 point if T2-SLL is observed on \u0026lt;50% of the surface, (c) 2 points if T2-SLL is observed on ≥50% but not the entire surface, and (d) 3 points if thin T2-SLL observed on the entire surface\u003c/p\u003e","description":"","filename":"PonsT2WIFig4.png","url":"https://assets-eu.researchsquare.com/files/rs-5695756/v1/c6e71ad9f17fb4240311b473.png"},{"id":73757451,"identity":"582f7571-bde2-4b86-825a-09904751df4b","added_by":"auto","created_at":"2025-01-14 10:53:09","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":15445,"visible":true,"origin":"","legend":"\u003cp\u003eAge-dependent differences in the frequency of T2 superficial localized low intensity (T2-SLL)\u003c/p\u003e\n\u003cp\u003eThe median summed T2-SLL score increased with age. However, the Kruskal-Wallis test showed no significant differences between age groups (\u003cem\u003eP \u003c/em\u003e= 0.24).\u003c/p\u003e","description":"","filename":"PonsT2WIFig51.png","url":"https://assets-eu.researchsquare.com/files/rs-5695756/v1/376c82b42a31c9567b1021c8.png"},{"id":73757455,"identity":"785a2979-cb00-452a-a01b-4e68fe60527d","added_by":"auto","created_at":"2025-01-14 10:53:09","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":625396,"visible":true,"origin":"","legend":"\u003cp\u003eThe\u003cstrong\u003e \u003c/strong\u003emagnetic susceptibility effect of T2 superficial localized low intensity (T2-SLL) observed on T2*WI. In T2*WI, a superficial localized low-signal (SLL) intensity was observed, similar to T2WI. These SLL regions thickened and became more pronounced as the TE lengthened (➠). The vessels also enlarged as the TE lengthened, similar to SLL (➤). From these findings, it was determined that T2-SLL exhibits the magnetic susceptibility effect\u003c/p\u003e","description":"","filename":"PonsT2WIFig61.png","url":"https://assets-eu.researchsquare.com/files/rs-5695756/v1/1f44ef177ba99ac53f9d585e.png"},{"id":73758773,"identity":"f133d84b-8c8f-4b84-9288-0e9ede3a0b2c","added_by":"auto","created_at":"2025-01-14 11:09:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3645886,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5695756/v1/fd880e4d-9905-4a4d-8b0d-105a0ef0211f.pdf"},{"id":73756742,"identity":"ad855f00-913d-4dcf-9bfb-cb82c3137a62","added_by":"auto","created_at":"2025-01-14 10:45:09","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1257418,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Fig. 1 \u003c/strong\u003eExample of T2-SLL scoring. (a) midbrain, (b) upper pons (at the superior cerebellar peduncle level), (c) lower pons (at the middle cerebellar peduncle level), (d) medulla oblongata, (e) cerebellum (at the middle cerebellar peduncle level), and the temporal lobe\u003c/p\u003e","description":"","filename":"PonsT2WIFigSupp1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5695756/v1/62f02c460dabfd0114bdb667.pdf"},{"id":73756750,"identity":"d417e8ff-f5be-4206-82b7-b52df44777d0","added_by":"auto","created_at":"2025-01-14 10:45:09","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":58510,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Fig. 2 \u003c/strong\u003eMedian and interquartile range of T2 superficial localized low intensity in 22 brain areas\u003c/p\u003e","description":"","filename":"PonsT2WIFigSupp2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5695756/v1/0736af1fa5a5dbf1a108aac5.pdf"},{"id":73756747,"identity":"00bece40-a146-46ba-aa48-be8fc10f960a","added_by":"auto","created_at":"2025-01-14 10:45:09","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":754517,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Fig. 3 \u003c/strong\u003eT2-SLL distribution on high-resolution T2WI from the experimental MRI study component. (a) midbrain, (b) upper pons (at the superior cerebellar peduncle level), (c) lower pons (at the middle cerebellar peduncle level), (d) medulla oblongata, (e) cerebellum (at the middle cerebellar peduncle level), and the temporal lobe\u003c/p\u003e","description":"","filename":"PonsT2WIFigSupp3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5695756/v1/6cc2e93a0abfc985d1c7b052.pdf"},{"id":73757438,"identity":"8e05f2bb-3817-4173-b948-298e793bad9a","added_by":"auto","created_at":"2025-01-14 10:53:09","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":422628,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Fig. 4 \u003c/strong\u003eChemical shift effect of T2-SLL\u003c/p\u003e","description":"","filename":"PonsT2WIFigSupp4.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5695756/v1/63c34576f82fc70aa99bffad.pdf"},{"id":73757441,"identity":"2231e16d-d535-491a-aff0-a0831a8e3ceb","added_by":"auto","created_at":"2025-01-14 10:53:09","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":662032,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Fig. 5 \u003c/strong\u003ePartial volume effect of T2-SLL. T2-SLL became unclear when the slice thickness was increased from 2 mm to 5 mm and 10 mm\u003c/p\u003e","description":"","filename":"PonsT2WIFigSupp5.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5695756/v1/3da8acb7678f7ec720dd12e8.pdf"},{"id":73758146,"identity":"1f29bdb9-0358-4106-95c3-2cb01e9027d0","added_by":"auto","created_at":"2025-01-14 11:01:09","extension":"pdf","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":399855,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Fig. 6 \u003c/strong\u003eComparison of T2-SLL between three different MRI scanners. T2-SLL was observed on T2WI using all three scanners\u003c/p\u003e","description":"","filename":"PonsT2WIFigSupp6.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5695756/v1/23b2ca0d85b85344fa90c475.pdf"},{"id":73756748,"identity":"6c4692ae-03d3-485a-a792-7c75ce50d6df","added_by":"auto","created_at":"2025-01-14 10:45:09","extension":"pdf","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":82549,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Table 1. Parameters of three different MRI scnanner axial spin echo T2WI\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"PonsT2WITableSupp1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5695756/v1/ecc9c31771acabaffe90f479.pdf"},{"id":73756755,"identity":"4aab3e20-dfa0-41f2-bf98-3d0316230746","added_by":"auto","created_at":"2025-01-14 10:45:09","extension":"pdf","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":54074,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Table 2. Details of the diagnosis of 114 participants\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"PonsT2WITableSupp2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5695756/v1/a95a8cba7a8a6bf0eedd2628.pdf"},{"id":73756751,"identity":"b4d9a75f-896e-4927-9e83-2b67f91a0550","added_by":"auto","created_at":"2025-01-14 10:45:09","extension":"pdf","order_by":9,"title":"","display":"","copyAsset":false,"role":"supplement","size":58863,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Table 3. Cross-tabulation table of T2-SLL scoreing between two radiologists\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"PonsT2WITableSupp3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5695756/v1/9d47ed76d66db8092ef37d13.pdf"},{"id":73756764,"identity":"ac4e738f-007d-4e5f-a332-cb384565f88b","added_by":"auto","created_at":"2025-01-14 10:45:10","extension":"pdf","order_by":10,"title":"","display":"","copyAsset":false,"role":"supplement","size":121693,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Table 4. Post-hoc Scheffe's paired comparison for T2-SLL score difference among twenty-two areas\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"PonsT2WITableSupp4.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5695756/v1/202d46af1cc40dd2cf512302.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eA Low-intensity Rim on T2-weighted Brainstem Imaging is a Normal Finding and a Mimicker of Superficial Siderosis\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eSuperficial siderosis (SS) is characterized by linear hemosiderin deposits in the subpial layer of the central nervous system, resulting from chronic bleeding into the subarachnoid space [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR32\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. SS can be divided into infra- and supratentorial subtypes [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Supratentorial SS is primarily caused by cerebral amyloid angiopathy, whereas infratentorial SS is primarily caused by spinal dural abnormalities and cerebrospinal fluid (CSF) leakage [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Infratentorial SS is most commonly identified on magnetic resonance imaging (MRI), with a rim of low intensity in the brainstem, cerebellum, and spinal cord observed on T2-weighted imaging (T2WI), T2*WI, and susceptibility-weighted imaging [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Infratentorial SS presents with nonspecific symptoms and can progress if left untreated [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Therefore, an early MRI-based diagnosis is imperative.\u003c/p\u003e \u003cp\u003eAt our institution, we have commonly observed a rim of superficial low intensity, mainly localized to the midbrain and pons, on screening T2WI of asymptomatic patients and in all age groups, including children, adults, and older adults (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA), as well as on T2WI of symptomatic SS patients (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). Thus, this localized rim of low intensity may be a normal phenomenon and not evidence of infratentorial SS. We refer to this phenomenon as T2 superficial localized low intensity (T2-SLL). To date, no studies have examined T2-SLL; therefore, the present study aimed to be the first to determine the incidence and causes of T2-SLL.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis study combined a retrospective observational study component and a single-case experimental study component. The study protocol was approved by the appropriate institutional ethics committee (file numbers: REC2024-071 and REC2024-072). For the retrospective study component, the requirement for written informed consent was waived due to data anonymization and the retrospective study design. Written informed consent was obtained from the volunteer for the single-case experimental study component. This study was conducted in accordance with the ethical standards of the institutional and/or national research committee and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eRetrospective Study Component\u003c/h3\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003eThe patient selection flowchart for this study is shown in Fig.\u0026nbsp;2. Patients who had undergone brain MRI examinations, including whole-brain axial spin-echo T2WI using a 3.0-T MR scanner (MAGNETOM VIDA; Siemens Healthineers, Erlangen, Germany) at our institution between June 2024 and July 2024 were selected from the database. Since brain MRIs of neonates and infants differ from those of older age groups [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e9\u003c/span\u003e], participants had to be at least 1 year of age at the time of the MRI examination to be considered eligible for inclusion. MRI scans with artifacts, including metal or motion, were excluded. Additionally, participants with lesions in any of the 22 evaluated brain areas were excluded.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eMRI\u003c/h3\u003e\n\u003cp\u003eWhole-brain axial spin-echo T2WI was acquired using clinical imaging sequences. The axial plane extended from the anterior commissure to the orbitomeatal line (OM) line. Representative T2WI parameters are listed 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\u003eRepresentative parameters of axial spin echo T2WI in clinical use at our institution\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMR Scanner\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMAGNETOM VIDA\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSiemens Healthineers\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMagnetic field\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.0-Tesla\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4500\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e104\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e160\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMatrix\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e294*368\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNEX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSlice thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 mm\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSlice gap\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 mm\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eField of View\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e220 mm\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eT2WI, T2 weighted image; TR, Repetition Time; TE, Echo Time; FA, Flip Angle; NEX, Number of Excitations; FOV, Field of View\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eImaging Analysis\u003c/h3\u003e\n\u003cp\u003eFor the imaging analysis, T2-SLL was defined as a low signal intensity on the brain surface, similar to or lower than that of the substantia nigra (SN), which has physiological iron deposition [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and mainly shows a low signal intensity on T2WI [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Iron deposition in the SN is completed earlier than in the globus pallidus, putamen, and caudate nucleus and is less affected by aging [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Therefore, the SN was used as a reference region to identify a low T2WI signal intensity.\u003c/p\u003e \u003cp\u003eVisual estimation was performed independently by two radiologists (with 23 and 11 years of experience) who reviewed brain T2WI MRI scans using workstation software (EV Insite 4.2; PSP Corporation, Tokyo, Japan) to determine the presence of T2-SLL. To facilitate a comparison with the midbrain SN, reversed T2WI was also evaluated. The window level of the reversed T2WI was set near each participant\u0026rsquo;s SN signal value, and a narrow window width (approximately 150) was set.\u003c/p\u003e \u003cp\u003eThe presence of T2-SLL was evaluated at 22 locations within the following areas: lower midbrain, upper pons, lower pons, medulla oblongata, cerebellum, and temporal lobe. The locations in the midbrain, pons, and medulla oblongata were defined based on the cisterns and ventricles that encountered the brainstem. The cistern regions were defined based on a report by Morris et al.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. For the cerebellum, both the left and right cerebellar hemisphere surfaces were evaluated, and for the temporal lobe, the surfaces of the left and right temporal poles were assessed. Additional details of the evaluation sites are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eList of twenty-two areas to assess T2 superficial localized low intensity, and T2-SLL score of each areas\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eArea\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eContact cistern or ventricle\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eT2-SLL score\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eA. Lower midbrain: inferior colliculus level\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003emedian\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIQR\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003efrontal surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003einterpeduncular cistern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.0\u0026ndash;2.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eright frontolateral surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eright crural cistern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.0\u0026ndash;2.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eleft frontolateral surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eleft crural cistern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.0\u0026ndash;2.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eright lateral surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eright ambient cistern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.0\u0026ndash;2.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eleft lateral surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eleft ambient cistern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.0\u0026ndash;2.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eposterior surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003equadrigeminal cistern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u0026ndash;1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eB. Upper pons: superior cerebellar peduncle level\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003emedian\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eIQR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003efrontal surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eprepontine cistern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.0\u0026ndash;3.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eright lateral surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eright cerebellopontine angle cistern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.5\u0026ndash;2.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eleft lateral surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eleft cerebellopontine angle cistern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.0\u0026ndash;2.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eposterior surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eforth ventricle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.5\u0026ndash;1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eC. Lower pons: middle cerebellar peduncle level\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003emedian\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eIQR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003efrontal surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eprepontine cistern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.0\u0026ndash;2.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eright lateral surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eright cerebellopontine angle cistern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.0\u0026ndash;2.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eleft lateral surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eleft cerebellopontine angle cistern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.0\u0026ndash;2.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eposterior surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eforth ventricle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.0\u0026ndash;1.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eD. Medulla oblongata: glossopharyngeal nerve root level\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003emedian\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eIQR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003efrontal surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epremedullary cistern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.0\u0026ndash;2.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eright lateral surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eright lateral cerebellomedullary cistern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.5\u0026ndash;1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eleft lateral surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eright lateral cerebellomedullary cistern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.5\u0026ndash;1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eposterior surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eforth ventricle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u0026ndash;1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eE. Others\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003elocation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003emedian\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eIQR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eright temporal lobe surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eright temporal pole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u0026ndash;0.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eleft temporal lobe surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eleft temporal pole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u0026ndash;0.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eright cerebellar hemisphere surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003emiddle cerebellar peduncle level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u0026ndash;0.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eleft cerebellar hemisphere surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003emiddle cerebellar peduncle level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u0026ndash;0.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eIQR, interquartile range;\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eT2-SLL was evaluated for each of the 22 areas using the following scoring system: 0 points for the absence of T2-SLL, 1 point for \u0026lt;\u0026thinsp;50% of the surface, 2 points for \u0026ge;\u0026thinsp;50% of the surface but not the entire surface, and 3 points for the entire surface (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003e). A scoring example is shown in Supplementary Fig.\u0026nbsp;1. After assessing inter-tester agreement, the analysts\u0026rsquo; scores for each area were averaged. Then, each participant\u0026rsquo;s T2-SLL scores in the 22 areas were summed (summed T2-SLL score).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eNonparametric statistical methods were employed because the Shapiro\u0026ndash;Wilk test revealed a non-normal distribution of T2-SLL scores. Inter-tester agreement was assessed using weighted kappa statistics. The κ values were interpreted as follows: poor (κ\u0026thinsp;=\u0026thinsp;0.0), small/slight (κ\u0026thinsp;=\u0026thinsp;0.0\u0026ndash;0.20), fair (κ\u0026thinsp;=\u0026thinsp;0.21\u0026ndash;0.40), moderate (κ\u0026thinsp;=\u0026thinsp;0.41\u0026ndash;0.60), substantial (κ\u0026thinsp;=\u0026thinsp;0.61\u0026ndash;0.80), and almost perfect (κ\u0026thinsp;=\u0026thinsp;0.81\u0026ndash;1.00) [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The Friedman test was performed to evaluate differences in the T2-SLL scores of the 22 areas, and the Scheff\u0026eacute;\u0026rsquo;s post-hoc test was performed for multiple comparisons. To confirm age-dependent differences in summed T2-SLL scores, participants were categorized into three subgroups: children (under 18 years), adults (18 to under 65 years), and older adults (\u0026ge;\u0026thinsp;65 years). The summed T2-SLL scores of the subgroups were compared using the Kruskal-Wallis test, and the Scheff\u0026eacute;\u0026rsquo;s post-hoc test was performed to specifically compare two groups.\u003c/p\u003e \u003cp\u003eAll statistical analyses were performed using a commercial software program (Bell Curve for Excel 4.07; Social Survey Research Information, Tokyo, Japan). Statistical significance was set at \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSingle-case Experimental Study Component\u003c/h3\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eParticipant\u003c/h2\u003e \u003cp\u003eThe participant was a 40-year-old, healthy male volunteer without a history of neurological diseases, including stroke, subarachnoid hemorrhage, cerebral hemorrhage, or head injury, and without neurological symptoms, including those suggestive of cerebrospinal fluid hypovolemia or SS, such as headaches [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e16\u003c/span\u003e], ataxia [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e17\u003c/span\u003e], or hearing loss [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. MRI was performed to evaluate the effects of chemical shifts and magnetic susceptibility on T2-SLL.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eMRI Scanner\u003c/h2\u003e \u003cp\u003eBrain MRI was performed using a 3.0-T MR scanner (MAGNETOM VIDA; Siemens Healthineers) and a 64-channel head coil.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eDistribution of T2-SLL\u003c/h2\u003e \u003cp\u003eTo investigate the distribution of T2-SLL, brainstem-focused, high-resolution T2WI was performed using the following sequences: axial T2WI; repetition time (TR)/echo time (TE), 6230/99 ms; flip angle, 147\u0026deg;; matrix, 288 \u0026times; 288; field of view (FOV), 160 mm; slice thickness, 2 mm, frequency encoding, right-left (RL) direction; and bandwidth, 395 Hz/pix. Deep Resolve (Siemens Healthineers), a deep-learning reconstruction method, was applied to denoise and improve resolution. The distribution of T2-SLL was assessed in the same 22 areas used for the retrospective study component.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eChemical Shift Effect\u003c/h2\u003e \u003cp\u003eFirst, axial T2WI (TR/ TE, 4500/104 ms; flip angle, 160\u0026deg;; matrix, 368 \u0026times; 294; FOV, 220 mm; slice thickness, 5 mm; frequency encoding, RL direction; bandwidth, 400 Hz/pix) was performed as a standard. To avoid the influence of filters, images were created without applying filters except for the sensitivity correction filter, which corrects for contrast irregularities.\u003c/p\u003e \u003cp\u003eTo assess the effect of the chemical shift on T2-SLL, the bandwidths and encoding directions were altered from those of the standard T2WI. The bandwidth was adjusted to 200 and 100 Hz/pix to determine whether the T2-SLL varied in each image, while the other T2WI parameters remained unchanged. Second, the encoding direction was modified to left-right, anterior-posterior, and posterior-anterior, while the other T2WI parameters, including the bandwidth, were consistent with the standard T2WI.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eMagnetic Susceptibility Effect\u003c/h2\u003e \u003cp\u003eTo determine whether T2-SLL exhibits the magnetic susceptibility effect, the TE of T2*WI was varied to determine whether any alterations in the size of the T2-SLL occurred [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. First, axial and sagittal T2*WI (TR/TE, 1800/10 ms; flip angle, 20\u0026deg;; matrix, 224 \u0026times; 224; FOV, 220 mm; slice thickness, 2 mm) was performed as a standard T2*WI. Subsequently, the TE was changed to 20, 30, 40, and 50 ms, while the other T2*WI parameters were unchanged.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003ePartial Volume Effect (PVE)\u003c/h2\u003e \u003cp\u003eTo assess the PVE on T2-SLL, the slice thickness was changed to 2, 5, and 10 mm, while the other parameters (TR/TE, 4500/103 ms; flip angle, 160\u0026deg;; matrix, 320 \u0026times; 320; FOV, 160 mm; bandwidth, 400 Hz/pix) remained unchanged.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eOther MRI Sequences\u003c/h2\u003e \u003cp\u003eT1-weighted imaging (T1WI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), diffusion-weighted imaging (DWI), and time-of-flight magnetic resonance angiography (TOF MRA) were also performed to rule out neurological diseases, such as brain infarctions, subdural hematomas, or brain tumors.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eComparison Between MRI Scanners\u003c/h2\u003e \u003cp\u003eTo confirm that T2-SLL is not dependent on a specific MRI scanner, brain T2WI was performed using two additional 1.5-T MR scanners (Vantage Fortian; Canon Medical Systems, Otawara, Japan and Optima 450w; GE Healthcare, Milwaukee, WI, USA). Axial spin-echo T2-weighted brain images were acquired using clinical imaging sequences optimized for each MRI system, as routinely performed at our institution. The axial plane was aligned along the OM line. These T2WI parameters are listed in Supplementary Table\u0026nbsp;1.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003eRetrospective Study Component\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eGeneral Information about Enrolled Participants\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, 126 patients met the inclusion criteria. However, per the exclusion criteria, patients with lesions in the 22 evaluation areas were excluded, including those with brain infarctions (n=2), brain tumor invasion (n=5), post-brain tumor resections (n=4), or large aneurysms (n=1). No participants were excluded due to motion or metal artifacts. Overall, the present study included 114 patients (68 males and 46 females; mean age: 59.1; range, 6–84 years), with eight children (three males, mean age: 13.4 years), 54 adults (32 males, mean age: 49.4 years), and 52 older adults (33 males, mean age: 76.1 years). Details about participants’ diagnoses are shown in Supplementary Table 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eInter-tester Agreement \u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eModerate inter-tester agreement for T2-SLL scoring existed between the two radiologists, with a κ=0.556 (95% confidence interval [CI] 0.527–0.586). A cross-tabulation table with the radiologists’ T2-SLL scores is shown in Supplementary Table 3.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eLocation and Incidence of T2-SLL\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eT2-SLL was observed in all 114 participants, though its extent varied among individuals. Among the 22 areas, the median and interquartile range (IQR) of the T2-SLL score for the frontal surface of the upper pons was the highest (2.0; IQR 2.0–3.0). T2-SLL was also identified in a wide range of midbrain and upper pons areas other than the posterior surface of the lower midbrain (0.5; IQR 0.0–1.0) and upper pons (1.0; IQR 0.5–1.0). T2-SLL was identified less frequently on the surfaces of the temporal lobes and cerebellar hemispheres than in other areas (Table 2, Supplementary Figure 1). The Friedman test revealed a significant difference in T2-SLL scores according to area (\u003cem\u003eP \u003c/em\u003e\u0026lt; 0.001). Scheffé’s post-hoc test results are shown in Supplementary Table 2. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAge-dependent Differences in the Frequency of T2-SLL\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median summed T2-SLL score increased with age. The median for each age group was 24.3 (IQR 22.9–25.8) for children, 25.8 (IQR 23.5–27.0) for adults, and 26.0 (IQR 24.0–28.0) for older adults (Figure 5). However, the Kruskal-Wallis test revealed no significant differences in the summed T2-SLL scores according to age group (\u003cem\u003eP \u003c/em\u003e= 0.24).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSingle-case Experimental Study Component\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eDistribution of T2-SLL\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eT2-SLL was observed on the entire frontal surface of the upper pons and the left lateral surface of the lower pons on a high-resolution T2WI of the participant. T2-SLL was also observed extensively in the midbrain and pons but not on the surfaces of the temporal lobes or cerebellar hemispheres (Supplementary Figure 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eChemical Shift Effect\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo differences in T2-SLL were observed between T2WI images with different bandwidths or encoding directions (Supplementary Figure 4). Therefore, T2-SLL was considered unrelated to the chemical shift.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eMagnetic Susceptibility Effect \u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOn standard T2*WI (TE = 10), T2-SLL was observed in the same areas as on T2WI, and these regions thickened as the TE lengthened (Figure 6). In addition, the vessels observed in the same slice enlarged as the TE lengthened. Therefore, T2-SLL was considered to exhibit the magnetic susceptibility effect.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePVE \u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eT2-SLL became unclear when the slice thickness increased from 2 mm to 5 mm and 10 mm (Supplementary Figure 5).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eOther MRI Findings\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo neurological diseases were identified using other MRI sequences, including T2WI, T2*WI, T1WI, T2-FLAIR, DWI, or TOF MRA (data not presented).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eComparison Between Different MRI Scanners\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo significant differences in T2-SLL were observed between T2WI performed using the three different MRI scanners (Supplementary Figure 6). \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cbr\u003e \u003c/strong\u003e\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis combined retrospective observational and single-case experimental study investigated the frequency and causes of T2-SLL. Specifically, T2-SLL was commonly observed on the lateral and frontal sides of the midbrain and pons and was found to exhibit the magnetic susceptibility effect.\u003c/p\u003e\n\u003cp\u003eNo previous studies have been conducted on T2-SLL to date. However, a magnetic susceptibility map from a previous 7T-MRI study confirmed the magnetic susceptibility effect on the surface of the brainstem, similar to the experimental study results observed in the present study [20]. In the previous study, the magnetic susceptibility effect was clearly observed at the upper pons on the frontal and lateral surfaces and was attributed to a magnetization effect related to the fibers of the middle cerebellar peduncle. However, at the lower pons level, the middle cerebellar peduncle showed no high magnetic susceptibility. Moreover, in tensor imaging conducted simultaneously in the previous study, the fibers of the cerebellar peduncle were depicted; however, they were observed over a wider range than the range where the magnetic susceptibility effect was confirmed. The magnetic susceptibility effect was localized to the surface; therefore, it is unlikely that T2-SLL and surface magnetic susceptibility effects are associated with nerve fibers.\u003c/p\u003e\n\u003cp\u003eWhen T2WI shows a low signal intensity, the following factors are potential causes: gadolinium, hemoglobin, hemosiderin, melanin, mucous, high cellular density, mineral substances (such as iron, copper, and calcium), flow voids due to blood or CSF flow, and air-containing spaces [21]. Hemoglobin, hemosiderin, melanin, minerals, and blood in the vessels exhibit the magnetic susceptibility effect [22]. In the present study, T2-SLL was observed across a wide range of age groups and in asymptomatic participants. Therefore, this phenomenon cannot be regarded as a lesion, and hemosiderin deposition (i.e., siderosis) is unlikely. In the brain, neuromelanin is present in the SN and locus coeruleus [23] but does not exhibit a superficial brainstem-spreading distribution. Therefore, T2-SLL may instead be related to blood vessels or mineral deposition. \u003c/p\u003e\n\u003cp\u003eAlthough no significant differences were observed, the summed T2-SLL scores of children tended to be lower than those of adults or older adults in the present study. Therefore, the possibility that age-related mineral deposits are causing T2-SLL cannot be ruled out. Mineral deposition can be observed using Perls’ Prussian blue staining for iron [24], rhodanine staining for copper [25], and Von Kossa staining for calcium [26]. However, to date, physiological mineral deposition in the brainstem has not been reported.\u003c/p\u003e\n\u003cp\u003eNumerous minute arteries and veins develop in the brainstem. For example, the pons has numerous arterial and venous networks that run along the surface of the brain and connect to the capillaries [27, 28]. These blood vessels may be observable as superficial low-intensity vessels exhibiting the magnetic susceptibility effect. In the present study, higher T2-SLL scores were observed on the frontal sides of the pons and midbrain. Conversely, the temporal lobe and cerebellar hemisphere surfaces exhibited lower T2-SLL scores. This discrepancy may be attributable to differences in the development of the associated blood vessels on the brain surface [29]. The frontal side of the brainstem is mainly composed of white matter, whereas the areas underlying the surfaces of the temporal lobes and cerebellar hemispheres are mainly composed of gray matter. Therefore, the structure of the capillaries on the surface may differ depending on whether the structure that exists directly below them is either white or gray matter. However, no study has specifically examined the degree of blood vessel development on the brain surface. Further anatomical and histological studies are required to confirm these findings.\u003c/p\u003e\n\u003cp\u003eIn the retrospective observational study component, there was a moderate inter-tester agreement for T2-SLL scoring. However, some cases showed larger discrepancies in T2-SLL scoring between the two radiologists, which may be related to the PVE and slice thickness [30]. The midbrain and pons are thicker regions in the cephalocaudal direction, and the center of the slice may not always align with the center of other key structures, such as the inferior colliculus or superior cerebellar peduncle, on a 5-mm-thick image. Therefore, for cases with large discrepancies in the two radiologists’ evaluations, it is possible that the cross-sections in which the evaluations were performed were different. Moreover, the brainstem region has a complex structure, and thick-slice images may obscure the limbus due to the PVE. The 5-mm-thick images were more prone to PVE, and a one-slice deviation could have led to large differences in the evaluations. Indeed, in the experimental study, T2-SLL was observed evenly and extensively around the ventral side of the pons on 2 mm-thickness, high-resolution T2WI. However, T2-SLL became more obscured as the slices became thicker. Therefore, further studies with thinner slices are required to confirm a more accurate normal distribution of T2-SLL.\u003c/p\u003e\n\u003cp\u003eAlthough no significant differences were observed in the present study, the T2-SLL scores tended to be lower in children, which may be related to the PVE. Since children have smaller head sizes [31], PVE is more likely to occur when imaging is performed using the same FOV and voxel size parameters as in adults. In the single-case experimental study component, we observed uniform T2-SLL in the pons and midbrain using 2-mm imaging. In contrast, when the slice thickness was increased, T2-SLL became unclear. The PVE may, therefore, explain the tendency toward lower T2-SLL scores in children.\u003c/p\u003e\n\u003cp\u003eThe strength of the present study is that it was the first to focus on T2-SLL and to investigate its frequency and causes. However, it also had several limitations. First, both study components involved a single center. Second, contrast enhancement was not performed in the present study. At our institution, unenhanced T1WI is performed using a fast-spin echo sequence, whereas contrast-enhanced T1WI is routinely performed using a gradient echo sequence. To accurately determine the contrast effect, pre- and post-enhanced T1WI must be performed using the same sequence. Moreover, performing contrast-enhanced MRI in healthy volunteers is not recommended due to the risk of side effects. However, further studies, including contrast studies, are necessary to confirm that T2-SLL originates from small vessels.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eThis study demonstrated that a rim of a superficial low-intensity signal on T2WI can be observed in the midbrain and pons of healthy individuals and that these areas exhibit the magnetic susceptibility effect. T2-SLL can, therefore, be considered a normal structure, possibly associated with small surface blood vessels. When diagnosing SS using T2WI, it is important to consider the possibility of misidentifying T2-SLL as early-stage SS.\u003c/p\u003e"},{"header":"Statements and Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u003c/strong\u003e The authors declare no conflicts of interest related to the content of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study combined a retrospective observational study component and a single-case experimental study component. The study protocol was approved by the appropriate institutional ethics committee (file numbers\u0026nbsp;REC2024-072 [retrospective observational study]\u0026nbsp;and REC2024-071 [single-case experimental study]) and conducted in accordance with the ethical standards of the institutional and/or national research committee and the 1964 Helsinki Declaration and its later amendments, or comparable ethical standards.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor the retrospective study component, the requirement for written informed consent was waived due to data anonymization and the retrospective study design. Written informed consent was obtained from the volunteer for the single-case experimental study component.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKumar N, Cohen-Gadol AA, Wright RA, et al (2006) Superficial siderosis. Neurology 66:1144\u0026ndash;1152. https://doi.org/10.1212/01.wnl.0000208510.76323.5b\u003c/li\u003e\n\u003cli\u003eKumar N (2021) Superficial Siderosis: A Clinical Review. Ann Neurol 89:1068\u0026ndash;1079. https://doi.org/10.1002/ana.26083\u003c/li\u003e\n\u003cli\u003eWeidauer S, Neuhaus E, Hattingen E (2023) Cerebral Superficial Siderosis : Etiology, Neuroradiological Features and Clinical Findings. Clin Neuroradiol 33:293\u0026ndash;306. https://doi.org/10.1007/s00062-022-01231-5\u003c/li\u003e\n\u003cli\u003eSchievink WI (2024) Superficial siderosis and the dura. Eur J Neurol 31:e16182. https://doi.org/10.1111/ene.16182\u003c/li\u003e\n\u003cli\u003eKharytaniuk N, Cowley P, Sayal P, et al (2022) Classical infratentorial superficial siderosis of the central nervous system: pathophysiology, clinical features and management. Pract Neurol 22:274\u0026ndash;284. https://doi.org/10.1136/practneurol-2021-003324\u003c/li\u003e\n\u003cli\u003eWilson D, Chatterjee F, Farmer SF, et al (2017) Infratentorial superficial siderosis: Classification, diagnostic criteria, and rational investigation pathway. Ann Neurol 81:333\u0026ndash;343. https://doi.org/10.1002/ana.24850\u003c/li\u003e\n\u003cli\u003eEl Rahal A, Haupt B, Fung C, et al (2024) Surgical closure of spinal cerebrospinal fluid leaks improves symptoms in patients with superficial siderosis. Eur J Neurol 31:1\u0026ndash;9. https://doi.org/10.1111/ene.16122\u003c/li\u003e\n\u003cli\u003eKharytaniuk N, Mazaheri AA, Pavlou M, et al (2022) Health-Related Quality of Life in Adults with Classical Infratentorial Superficial Siderosis: A Cross-sectional Study. Neurology 99:E2201\u0026ndash;E2211. https://doi.org/10.1212/WNL.0000000000201115\u003c/li\u003e\n\u003cli\u003eBarkovich AJ (2000) Concepts of myelin and myelination in neuroradiology. AJNR Am J Neuroradiol 21:1099\u0026ndash;1109\u003c/li\u003e\n\u003cli\u003eIto H, Kawaguchi H, Kodaka F, et al (2017) Normative data of dopaminergic neurotransmission functions in substantia nigra measured with MRI and PET: Neuromelanin, dopamine synthesis, dopamine transporters, and dopamine D2 receptors. Neuroimage 158:12\u0026ndash;17. https://doi.org/10.1016/j.neuroimage.2017.06.066\u003c/li\u003e\n\u003cli\u003eAoki S, Okada Y, Nishimura K, et al (1989) Normal deposition of brain iron in childhood and adolescence: MR imaging at 1.5 T. Radiology 172:381\u0026ndash;385. https://doi.org/10.1148/radiology.172.2.2748819\u003c/li\u003e\n\u003cli\u003eAquino D, Bizzi A, Grisoli M, et al (2009) Age-related iron deposition in the basal ganglia: quantitative analysis in healthy subjects. Radiology 252:165\u0026ndash;172. https://doi.org/10.1148/radiol.2522081399\u003c/li\u003e\n\u003cli\u003eMorris JA, Gilbert BC, Parker WT, Forseen SE (2022) Anatomy of the Ventricles, Subarachnoid Spaces, and Meninges. Neuroimaging Clin N Am 32:577\u0026ndash;601. https://doi.org/10.1016/j.nic.2022.04.005\u003c/li\u003e\n\u003cli\u003eCohen J (1968) Weighted kappa: Nominal scale agreement provision for scaled disagreement or partial credit. Psychol Bull 70:213\u0026ndash;220. https://doi.org/10.1037/h0026256\u003c/li\u003e\n\u003cli\u003eChung SJ, Kim JS, Lee MC (2000) Syndrome of cerebral spinal fluid hypovolemia: Clinical and imaging features and outcome. Neurology 55:1321\u0026ndash;1327. https://doi.org/10.1212/WNL.55.9.1321\u003c/li\u003e\n\u003cli\u003eSchievink WI (2006) Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA 295:2286\u0026ndash;2296. https://doi.org/10.1001/jama.295.19.2286\u003c/li\u003e\n\u003cli\u003eFearnley JM, Stevens JM, Rudge P (1995) Superficial siderosis of the central nervous system. Brain 118 (Pt 4):1051\u0026ndash;1066. https://doi.org/10.1093/brain/118.4.1051\u003c/li\u003e\n\u003cli\u003eChavhan GB, Babyn PS, Thomas B, et al (2009) Principles, techniques, and applications of T2*-based MR imaging and its special applications. Radiographics 29:1433\u0026ndash;1449. https://doi.org/10.1148/rg.295095034\u003c/li\u003e\n\u003cli\u003eYagi Y, Ohkubo M, Saito H, Kanazawa T (2022) A Method for Evaluating the T2*-weighting Effect in MRI. Japanese Journal of Radiological Technology 78:2022\u0026ndash;1189. https://doi.org/10.6009/jjrt.2022-1189\u003c/li\u003e\n\u003cli\u003eDeistung A, Sch\u0026auml;fer A, Schweser F, et al (2013) High-Resolution MR Imaging of the Human Brainstem In vivo at 7 Tesla. Front Hum Neurosci 7:710. https://doi.org/10.3389/fnhum.2013.00710\u003c/li\u003e\n\u003cli\u003eZimny A, Neska-Matuszewska M, Bladowska J, Sąsiadek MJ (2015) Intracranial lesions with low signal intensity on T2-weighted MR images - review of pathologies. Pol J Radiol 80:40\u0026ndash;50. https://doi.org/10.12659/PJR.892146\u003c/li\u003e\n\u003cli\u003eDuyn JH, Schenck J (2017) Contributions to magnetic susceptibility of brain tissue. NMR Biomed 30:1\u0026ndash;37. https://doi.org/10.1002/nbm.3546\u003c/li\u003e\n\u003cli\u003eZecca L, Tampellini D, Gerlach M, et al (2001) Substantia nigra neuromelanin: structure, synthesis, and molecular behaviour. Mol Pathol 54:414\u0026ndash;418 https://doi.org/10.1136/mp.54.6.414\u003c/li\u003e\n\u003cli\u003eKoeppen AH, Michael SC, Li D, et al (2008) The pathology of superficial siderosis of the central nervous system. Acta Neuropathol 116:371\u0026ndash;382. https://doi.org/10.1007/s00401-008-0421-z\u003c/li\u003e\n\u003cli\u003ePal A, Badyal RK, Vasishta RK, et al (2013) Biochemical, histological, and memory impairment effects of chronic copper toxicity: a model for non-Wilsonian brain copper toxicosis in Wistar rat. Biol Trace Elem Res 153:257\u0026ndash;268. https://doi.org/10.1007/s12011-013-9665-0\u003c/li\u003e\n\u003cli\u003eSchneider MR (2021) Von Kossa and his staining technique. Histochem Cell Biol 156:523\u0026ndash;526. https://doi.org/10.1007/s00418-021-02051-3\u003c/li\u003e\n\u003cli\u003eNaidich TP, Duvernoy HM, Delman BN, et al (2009) Vascularization of the Cerebellum and the Brain Stem. In: Duvernoy\u0026rsquo;s Atlas of the Human Brain Stem and Cerebellum. Springer, Vienna, pp 159\u0026ndash;217\u003c/li\u003e\n\u003cli\u003eTakahashi S (2011) Intracranial Arterial System: Infratentorial Arteries. In: Neurovascular Imaging. Springer London, London, pp 131\u0026ndash;188\u003c/li\u003e\n\u003cli\u003eViviani R (2016) A Digital Atlas of Middle to Large Brain Vessels and Their Relation to Cortical and Subcortical Structures. Front Neuroanat 10:12. https://doi.org/10.3389/fnana.2016.00012\u003c/li\u003e\n\u003cli\u003eTohka J, Zijdenbos A, Evans A (2004) Fast and robust parameter estimation for statistical partial volume models in brain MRI. Neuroimage 23:84\u0026ndash;97. https://doi.org/10.1016/j.neuroimage.2004.05.007\u003c/li\u003e\n\u003cli\u003eNellhaus G (1968) Head circumference from birth to eighteen years. Practical composite international and interracial graphs. Pediatrics 41:106\u0026ndash;114. https://doi.org/10.1542/peds.41.1.106\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003e\u003cspan lang=\"\"\u003eTable 1. Representative parameters of axial spin echo T2WI in clinical use at our institution\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"384\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cspan lang=\"\"\u003eMR Scanner\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 183px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cspan lang=\"\"\u003eMAGNETOM VIDA\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eVender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 183px;\"\u003e\n \u003cp\u003e\u003cspan lang=\"\"\u003eSiemens Healthineers\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eMagnetic field\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 183px;\"\u003e\n \u003cp\u003e\u003cspan lang=\"\"\u003e3.0-Tesla\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eTR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 183px;\"\u003e\n \u003cp\u003e4500\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 183px;\"\u003e\n \u003cp\u003e104\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eFA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 183px;\"\u003e\n \u003cp\u003e160\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eMatrix\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 183px;\"\u003e\n \u003cp\u003e\u003cspan lang=\"\"\u003e294*368\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eNEX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 183px;\"\u003e\n \u003cp\u003e\u003cspan lang=\"\"\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eSlice thickness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 183px;\"\u003e\n \u003cp\u003e5 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eSlice gap\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 183px;\"\u003e\n \u003cp\u003e\u003cspan lang=\"\"\u003e1 mm\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 201px;\"\u003e\n \u003cp\u003eField of View\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 183px;\"\u003e\n \u003cp\u003e\u003cspan lang=\"\"\u003e220 mm\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eT2WI, T2 weighted image; TR, Repetition Time; TE, Echo Time; FA, Flip Angle; NEX, Number of Excitations; FOV, Field of View\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan lang=\"\"\u003eTable 2. List of twenty-two areas to assess T2 superficial localized low intensity, and T2-SLL score of each areas\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"698\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eArea\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eContact cistern or ventricle\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT2-SLL score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 548px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eA. Lower midbrain: inferior colliculus level\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003emedian\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIQR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003efrontal surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003einterpeduncular cistern\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.0\u0026nbsp;\u0026ndash; 2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003eright frontolateral surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003eright crural cistern\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.0\u0026nbsp;\u0026ndash; 2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003eleft frontolateral surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003eleft crural cistern\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.0\u0026nbsp;\u0026ndash; 2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003eright lateral surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003eright ambient cistern\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e2.0\u0026nbsp;\u0026ndash; 2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003eleft lateral surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003eleft ambient cistern\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e2.0\u0026nbsp;\u0026ndash; 2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003eposterior surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003equadrigeminal cistern\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.0\u0026nbsp;\u0026ndash; 1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 548px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eB. Upper pons: superior cerebellar peduncle level\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003emedian\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIQR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003efrontal surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003eprepontine cistern\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e2.0\u0026nbsp;\u0026ndash; 3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003eright lateral surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003eright cerebellopontine angle cistern\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.5\u0026nbsp;\u0026ndash; 2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003eleft lateral surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003eleft cerebellopontine angle cistern\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e2.0\u0026nbsp;\u0026ndash; 2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003eposterior surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003eforth ventricle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.5\u0026nbsp;\u0026ndash; 1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 548px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eC. Lower pons: middle cerebellar peduncle level\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003emedian\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIQR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003efrontal surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003eprepontine cistern\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.0\u0026nbsp;\u0026ndash; 2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003eright lateral surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003eright cerebellopontine angle cistern\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.0\u0026nbsp;\u0026ndash; 2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003eleft lateral surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003eleft cerebellopontine angle cistern\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.0\u0026nbsp;\u0026ndash; 2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003eposterior surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003eforth ventricle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.0\u0026nbsp;\u0026ndash; 1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 548px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eD. Medulla oblongata: glossopharyngeal nerve root level\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003emedian\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIQR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003efrontal surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003epremedullary cistern\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.0\u0026nbsp;\u0026ndash; 2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003eright lateral surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003eright lateral cerebellomedullary cistern\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.5\u0026nbsp;\u0026ndash; 1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003eleft lateral surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003eright lateral cerebellomedullary cistern\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.5\u0026nbsp;\u0026ndash; 1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003eposterior surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003eforth ventricle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.0\u0026nbsp;\u0026ndash; 1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 284px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eE. Others\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003e\u003cstrong\u003elocation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003emedian\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIQR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003eright temporal lobe surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003eright temporal pole\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.0\u0026nbsp;\u0026ndash;\u0026nbsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003eleft temporal lobe surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003eleft temporal pole\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.0\u0026nbsp;\u0026ndash;\u0026nbsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003eright cerebellar hemisphere surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003emiddle cerebellar peduncle level\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.0\u0026nbsp;\u0026ndash;\u0026nbsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 246px;\"\u003e\n \u003cp\u003eleft cerebellar hemisphere surface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 265px;\"\u003e\n \u003cp\u003emiddle cerebellar peduncle level\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.0\u0026nbsp;\u0026ndash;\u0026nbsp;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eIQR, interquartile range;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Fukushima Medical University","isAcceptedByJournal":false,"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":"superficial siderosis, brain stem, pons, magnetic susceptibility effect, partial volume effect, chemical shift effect","lastPublishedDoi":"10.21203/rs.3.rs-5695756/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5695756/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e In healthy participants, T2 superficial localized low intensity (T2-SLL) similar to superficial siderosis has been observed in the brainstem. This study aimed to determine the incidence and causes of T2-SLL.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e To determine the incidence, T2-weighted imaging (T2WI) was performed on 114 patients (68 males; mean age: 59.1 years) using a 3.0-T magnetic resonance (MR) scanner and visually assessed by two radiologists. T2-SLL presence in 22 brain areas was evaluated using the following system: 0 for absence, 1 for \u0026lt;50% surface, 2 for ≥50% but not the entirety, and 3 for the entirety. After assessing inter-rater agreement, the scores were averaged. To investigate the causes of T2-SLL, an experimental MR imaging (MRI) was performed on a healthy male volunteer. To evaluate the chemical shift effect, the bandwidth and encoding direction were modified. To assess the magnetic susceptibility effect, T2*WI was performed using varying echo times (TEs).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eA moderate inter-rater score agreement (κ=0.556) was observed. T2-SLL was identified in all participants and was most frequently observed on the frontal and lateral sides of the midbrain and pons, with the highest occurrence on the frontal of the upper pons (median 2.0; interquartile range 2.0–3.0). In the experimental MRI, no differences in T2-SLL were observed across the varying bandwidths and encoding directions. However, the superficial low signal for T2WI thickened as the TE lengthened, similar to blood vessels, suggesting a magnetic susceptibility effect.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e T2-SLL can be regarded as a normal structure that may be associated with blood vessels.\u003c/p\u003e","manuscriptTitle":"A Low-intensity Rim on T2-weighted Brainstem Imaging is a Normal Finding and a Mimicker of Superficial Siderosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-14 10:45:04","doi":"10.21203/rs.3.rs-5695756/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":"20326fd1-e922-48ae-b044-28d9bff69e9b","owner":[],"postedDate":"January 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":42827046,"name":"Nuclear Medicine \u0026 Medical Imaging"}],"tags":[],"updatedAt":"2025-01-14T10:45:04+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-14 10:45:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5695756","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5695756","identity":"rs-5695756","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}