Correlation Between Vanishing White Matter Disease and Novel Heterozygous EIF2B3 Variants Using Next-Generation Sequencing: A Case Report

현성은,최병세,장자현,전인표,장대현,류주석 대한재활의학회 2019 Annals of Rehabilitation Medicine Vol.43 No.2

Vanishing white matter (VWM) disease is an autosomal recessive disorder that affects the central nervous system of a patient, and is caused by the development of pathogenic mutations in any of the EIF2B1-5 genes. Any dysfunction of the EIF2B1-5 gene encoded eIF2B causes stress-provoked episodic rapid neurological deterioration in the patient, followed by a chronic progressive disease course. We present the case of a patient with an infantile-onset VWM with the pre-described specific clinical course, subsequent neurological aggravation induced by each viral infection, and the noted consequent progression into a comatose state. Although the initial brain magnetic resonance imaging did not reveal specific pathognomonic signs of VWM to distinguish it from other types of demyelinating leukodystrophy, the next-generation sequencing studies identified heterozygous missense variants in EIF2B3, including a novel variant in exon 7 (C706G), as well as a 0.008% frequency reported variant in exon 2 (T89C). Hence, the characteristic of unbiased genomic sequencing can clinically affect patient care and decision-making, especially in terms of the consideration of genetic disorders such as leukoencephalopathy in pediatric patients.

Influence of B1-Inhomogeneity on Pharmacokinetic Modeling of Dynamic Contrast-Enhanced MRI: A Simulation Study

박범우,최병세,성유섭,우동철,심우현,김경원,최윤석,배상훈,서지연,조형준,김정곤 대한영상의학회 2017 Korean Journal of Radiology Vol.18 No.4

Objective: To simulate the B1-inhomogeneity-induced variation of pharmacokinetic parameters on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Materials and Methods: B1-inhomogeneity-induced flip angle (FA) variation was estimated in a phantom study. Monte Carlo simulation was performed to assess the FA-deviation-induced measurement error of the pre-contrast R1, contrast-enhancement ratio, Gd-concentration, and two-compartment pharmacokinetic parameters (Ktrans, ve, and vp). Results: B1-inhomogeneity resulted in -23–5% fluctuations (95% confidence interval [CI] of % error) of FA. The 95% CIs of FA-dependent % errors in the gray matter and blood were as follows: -16.7–61.8% and -16.7–61.8% for the pre-contrast R1, -1.0–0.3% and -5.2–1.3% for the contrast-enhancement ratio, and -14.2–58.1% and -14.1–57.8% for the Gd-concentration, respectively. These resulted in -43.1–48.4% error for Ktrans, -32.3–48.6% error for the ve, and -43.2–48.6% error for vp. The pre-contrast R1 was more vulnerable to FA error than the contrast-enhancement ratio, and was therefore a significant cause of the Gd-concentration error. For example, a -10% FA error led to a 23.6% deviation in the pre-contrast R1, -0.4% in the contrast-enhancement ratio, and 23.6% in the Gd-concentration. In a simulated condition with a 3% FA error in a target lesion and a -10% FA error in a feeding vessel, the % errors of the pharmacokinetic parameters were -23.7% for Ktrans, -23.7% for ve, and -23.7% for vp. Conclusion: Even a small degree of B1-inhomogeneity can cause a significant error in the measurement of pharmacokinetic parameters on DCE-MRI, while the vulnerability of the pre-contrast R1 calculations to FA deviations is a significant cause of the miscalculation.

Efficacy of Maximum Intensity Projection of Contrast-Enhanced 3D Turbo-Spin Echo Imaging with Improved Motion-Sensitized Driven-Equilibrium Preparation in the Detection of Brain Metastases

배윤정,최병세,이경미,윤연홍,선우준,정철규,김재형 대한영상의학회 2017 Korean Journal of Radiology Vol.18 No.4

Objective: To evaluate the diagnostic benefits of 5-mm maximum intensity projection of improved motion-sensitized driven-equilibrium prepared contrast-enhanced 3D T1-weighted turbo-spin echo imaging (MIP iMSDE-TSE) in the detection of brain metastases. The imaging technique was compared with 1-mm images of iMSDE-TSE (non-MIP iMSDE-TSE), 1-mm contrast-enhanced 3D T1-weighted gradient-echo imaging (non-MIP 3D-GRE), and 5-mm MIP 3D-GRE. Materials and Methods: From October 2014 to July 2015, 30 patients with 460 enhancing brain metastases (size > 3 mm, n = 150; size ≤ 3 mm, n = 310) were scanned with non-MIP iMSDE-TSE and non-MIP 3D-GRE. We then performed 5-mm MIP reconstruction of these images. Two independent neuroradiologists reviewed these four sequences. Their diagnostic performance was compared using the following parameters: sensitivity, reading time, and figure of merit (FOM) derived by jackknife alternative free-response receiver operating characteristic analysis. Interobserver agreement was also tested. Results: The mean FOM (all lesions, 0.984; lesions ≤ 3 mm, 0.980) and sensitivity ([reader 1: all lesions, 97.3%; lesions ≤ 3 mm, 96.2%], [reader 2: all lesions, 97.0%; lesions ≤ 3 mm, 95.8%]) of MIP iMSDE-TSE was comparable to the mean FOM (0.985, 0.977) and sensitivity ([reader 1: 96.7, 99.0%], [reader 2: 97, 95.3%]) of non-MIP iMSDE-TSE, but they were superior to those of non-MIP and MIP 3D-GREs (all, p < 0.001). The reading time of MIP iMSDE-TSE (reader 1: 47.7 ± 35.9 seconds; reader 2: 44.7 ± 23.6 seconds) was significantly shorter than that of non-MIP iMSDE-TSE (reader 1: 78.8 ± 43.7 seconds, p = 0.01; reader 2: 82.9 ± 39.9 seconds, p < 0.001). Interobserver agreement was excellent (κ > 0.75) for all lesions in both sequences. Conclusion: MIP iMSDE-TSE showed high detectability of brain metastases. Its detectability was comparable to that of non-MIP iMSDE-TSE, but it was superior to the detectability of non-MIP/MIP 3D-GREs. With a shorter reading time, the false-positive results of MIP iMSDE-TSE were greater. We suggest that MIP iMSDE-TSE can provide high diagnostic performance and low false-positive rates when combined with 1-mm sequences.

Differentiation of Deep Subcortical Infarction Using High-Resolution Vessel Wall MR Imaging of Middle Cerebral Artery

배윤정,최병세,정철규,윤연홍,선우준,배희준,김재형 대한영상의학회 2017 Korean Journal of Radiology Vol.18 No.6

Objective: To evaluate the utility of high-resolution vessel wall imaging (HR-VWI) of middle cerebral artery (MCA), and to compare HR-VWI findings between striatocapsular infarction (SC-I) and lenticulostriate infarction (LS-I). Materials and Methods: This retrospective study was approved by the Institutional Review Board, and informed consent was waived. From July 2009 to February 2012, 145 consecutive patients with deep subcortical infarctions (SC-I, n = 81; LS-I, n = 64) who underwent HR-VWI were included in this study. The degree of MCA stenosis and the characteristics of MCA plaque (presence, eccentricity, location, extent, T2-high signal intensity [T2-HSI], and plaque enhancement) were analyzed, and compared between SC-I and LS-I, using Fisher’s exact test. Results: Stenosis was more severe in SC-I than in LS-I (p = 0.040). MCA plaque was more frequent in SC-I than in LS-I (p = 0.028), having larger plaque extent (p = 0.001), more T2-HSI (p = 0.001), and more plaque enhancement (p = 0.002). The eccentricity and location of the plaque showed no significant difference between the two groups. Conclusion: Both SC-I and LS-I have similar HR-VWI findings of the MCA plaque, but SC-I had more frequent, larger plaques with greater T2-HSI and enhancement. This suggests that HR-VWI may have a promising role in assisting the differentiation of underlying pathophysiological mechanism between SC-I and LS-I.

Detection of Residual Brain Arteriovenous Malformations after Radiosurgery: Diagnostic Accuracy of Contrast-Enhanced Three-Dimensional Time of Flight MR Angiography at 3.0 Tesla

이경은,최충곤,최병세,이덕희,김상준,권도훈,최진우 대한영상의학회 2009 Korean Journal of Radiology Vol.10 No.4

Objective: Although three-dimensional time-of-flight magnetic resonance angiography (3D TOF-MRA) is used frequently as a follow-up tool to assess the response of arteriovenous malformations (AVMs) after radiosurgery, the diagnostic accuracy of 3D TOF-MRA is not well known. We evaluated the diagnostic accuracy of contrast-enhanced 3D TOF-MRA at 3.0 Tesla for the detection of residual AVMs. Materials and Methods: This study included 32 AVMs from 32 patients who had been treated with radiosurgery (males/females: 21/11; average patient age, 33.1 years). The time interval between radiosurgery and MRA was an average of 35.3 months (range, 12-88 months). Three-dimensional TOF-MRA was obtained at a magnetic field strength of 3.0 Tesla after infusion of contrast media, with a measured voxel size of 0.40 × 0.80 × 1.4 (0.45) ㎣ and a reconstructed voxel size of 0.27 × 0.27 × 0.70 (0.05) mm3 after zero-filling. X-ray angiography was performed as the reference of standard within six months after MRA (an average of two months). To determine the presence of a residual AVM, the source images of 3D TOF-MRA were independently reviewed, focusing on the presence of abnormally hyperintense fine tangled or tubular structures with continuity as seen on consecutive slices by two observers blinded to the X-ray angiography results. Results: A residual AVM was identified in 10 patients (10 of 32, 31%) on X-ray angiography. The inter-observer agreement for MRA was excellent (κ= 0.813). For the detection of a residual AVM after radiosurgery as determined by observer 1 and observer 2, the source images of MRA had an overall sensitivity of 100%/90% (10 of 10, 9 of 10), specificity of 68%/68% (15 of 22, 15 of 22), positive predictive value of 59%/56% (10 of 17, 9 of 16), negative predictive value of 100%/94% (15 of 15, 15 of 16) and diagnostic accuracy of 78%/75% (25 of 32, 24 of 32), respectively. Conclusion: The sensitivity of contrast-enhanced 3D TOF-MRA at 3.0 Tesla is high but the specificity is not sufficient for the detection of a residual AVM after radiosurgery.

외사시를 동반한 물무뇌증 1예

박채린,김남주,최병세,황정민,Chaerin Park,Nam Ju Kim,Byung Se Choi,Jeong-Min Hwang 대한안과학회 2010 대한안과학회지 Vol.51 No.7

Purpose: To report a large-angle exotropia, limited adduction, epiblepharon, high myopia and no pupillary light reflex in a patient with hydranencephaly. Case summary: A ten-year-old girl with mental retardation presented with exotropia. The patient could fix only with the right eye and was unable to follow with either eye. The Krimsky test revealed 95 prism diopters of exotropia, and adduction was severely limited in both eyes. Pupillary light reflex was absent in both eyes. Cycloplegic refraction showed high myopia in both eyes. Slit lamp examination revealed lower lid epiblepharon and inferior corneal opacity in the right eye. No abnormal findings in the fundus examination were detected. A computed tomogram of the brain showed that the cerebral hemispheres were replaced by a cystic space filled with cerebrospinal fluid, compatible with hydranencephaly. Recession of the lateral rectus muscle and resection of the medial rectus muscle with epiblepharon repair of the lower lid were performed in both eyes. One week postoperatively, the epiblepharon was corrected, and the Krimsky test showed 16 prism diopters of left intermittent exotropia at near. Conclusions: When a combined manifestation of mental retardation, limited adduction, no pupillary light reflex and a large-angle exotropia is present, the possibility of a congenital developmental anomaly of the central nervous system including hydranencephaly should be suspected.

The Susceptibility Vessel Sign of the Middle Cerebral Artery on the T2*-Weighted Gradient Echo Imaging: Semi-quantification to Predict the Response to Multimodal Intra-Arterial Thrombolysis

윤성원,정철규,최병세,김재형,권오기,한문구,배희준,권배주,한문희 대한영상의학회 2011 대한영상의학회지 Vol.64 No.1

Purpose: We wanted to determine whether or not the “susceptibility asymmetry index” (SAI) of acute stroke on the T2*-weighted image is related with successful recanalization using multimodal intra-arterial thrombolysis (IAT). Materials and Methods: The 81 patients who underwent multimodal IAT for middle cerebral artery (MCA) territory acute stroke were included in this retrospective study. The multimodal IAT included intra-arterial urokinase infusion, clot disruption by a microwire, microcatheter and balloon manipulation, and balloon angioplasty and/or stenting for the flow-limiting stenosis. The diameter of the susceptibility vessel sign was measured on the T2*-weighted gradient echo imaging (GRE), and the diameter of the contralateral normal MCA at the corresponding level was measured on magnetic resonance angiography (MRA); the ratio between these two diameters was defined as the susceptibility asymmetry index. The relation between the TICI (Thrombolysis In Cerebral Infarction) score of 2-3 after multimodal IAT and the SAI was assessed. The receiver operating characteristic (ROC) curve analysis was performed on the SAI to predict a TICI score of 2-3 after multimodal IAT. Results: The mean SAI of 81 patients was 1.66 ± 0.66. Seventy nine percent of the patients had a TICI of 2-3 after multimodal IAT. According to the ROC curve analysis, an SAI less than 1.3 was optimal for predicting the presence of stenotic lesion after recanalization (area under the curve: 0.821, sensitivity: 88.2%, specificity: 69.8%, p=0.0001), and the SAI ≤1.61 (area under the curve: 0.652, sensitivity: 60.9%, specificity: 70.6%, p=0.0226) could predict a TICI score of 2-3. The TICI score of 2-3 after multimodal IAT was achieved in 88.6% of the cases with a SAI ≤ 1.61 and in 67.6% of the cases with a SAI >1.61 (p=0.028). Conclusion: The lower SAI on T2*-GRE could predict stenotic lesion and successful recanalization after performing IAT.

Diagnosis of Vertebral Artery Ostial Stenosis on Contrast-Enhanced MR Angiography: Usefulness of a Thin-Slab MIP Technique

김선미,이덕희,최진우,최병세,인현신 대한자기공명의과학회 2011 Investigative Magnetic Resonance Imaging Vol.15 No.1

It is a well-known clinical fact that contrast-enhanced magnetic resonance angiography exaggerates vertebral arterial ostial stenosis and sometimes shows pseudostenosis. Considering the clinical significance of a lesion in the posterior circulation ischemia, the importance of an accurate imaging diagnosis of ostial stenosis should not be underestimated. We were able to differentiate pseudostenosis of the ostium from true stenosis using thin-slab maximum-intensity-projection(MIP)images which are thought to be helpful for minimizing standard full thickness MIP images.

Use of Self-Expanding Stents for the Treatment of Vertebral Artery Ostial Stenosis: a Single Center Experience

정선영,이덕희,최진우,최병세,인현신,김선미,최충곤,김상준,서대철 대한영상의학회 2010 Korean Journal of Radiology Vol.11 No.2

Objective: To evaluate our early experience using self-expanding stents to treat atherosclerotic vertebral artery ostial stenosis (VAOS), with respect to technical feasibility and clinical and imaging follow-up results. Materials and Methods: A total of 20 lesions in 20 patients underwent stenting of the VAOS using a self-expanding stent (Precise RX; Cordis Neurovascular, Miami Lakes, FL). Two patients were asymptomatic. We analyzed the technical success rate, causes of technical failure, occurrence of any vascular or neurological event, and the occurrence of any neurological abnormality or in-stent restenosis (ISR) seen on follow-up. The imaging follow-up was performed with Doppler ultrasound (DUS) as a primary screening modality. Results: One instance of technical failure was caused by failure of the guidewire passage. The stent diameter was 5 mm, and post-stenting balloon dilatations were necessary in all cases. Stent misplacement requiring placement of an additional stent occurred in four cases. Following a 14.8 month average clinical follow-up time, two patients showed anterior circulation ischemia, which was not attributed to the VAOS we treated. Following a 13.7 month average DUS follow-up, five patients showed a mild degree of diffuse or focal intimal thickening in the stent lumen; however, none of the stenosis showed luminal loss of more than 50% and no stent fracture was noted. Conclusion: The use of self-expanding stents for treating VAOS was technically feasible and helped to improve artery patency during our limited follow-up interval. Objective: To evaluate our early experience using self-expanding stents to treat atherosclerotic vertebral artery ostial stenosis (VAOS), with respect to technical feasibility and clinical and imaging follow-up results. Materials and Methods: A total of 20 lesions in 20 patients underwent stenting of the VAOS using a self-expanding stent (Precise RX; Cordis Neurovascular, Miami Lakes, FL). Two patients were asymptomatic. We analyzed the technical success rate, causes of technical failure, occurrence of any vascular or neurological event, and the occurrence of any neurological abnormality or in-stent restenosis (ISR) seen on follow-up. The imaging follow-up was performed with Doppler ultrasound (DUS) as a primary screening modality. Results: One instance of technical failure was caused by failure of the guidewire passage. The stent diameter was 5 mm, and post-stenting balloon dilatations were necessary in all cases. Stent misplacement requiring placement of an additional stent occurred in four cases. Following a 14.8 month average clinical follow-up time, two patients showed anterior circulation ischemia, which was not attributed to the VAOS we treated. Following a 13.7 month average DUS follow-up, five patients showed a mild degree of diffuse or focal intimal thickening in the stent lumen; however, none of the stenosis showed luminal loss of more than 50% and no stent fracture was noted. Conclusion: The use of self-expanding stents for treating VAOS was technically feasible and helped to improve artery patency during our limited follow-up interval.

Quantitative Magnetic Resonance Angiography in Internal Carotid Artery Occlusion with Primary Collateral Pathway

배윤정,Cheolkyu Jung,김재형,최병세,Eunhee Kim 대한뇌졸중학회 2015 Journal of stroke Vol.17 No.3

Background and Purpose Quantitative magnetic resonance angiography (Q-MRA) enables direct measurement of volume flow rate (VFR) of intracranial arteries. We aimed to evaluate the collateral flows in internal carotid artery (ICA) occlusion with primary collateral pathway via circle of Willis using Q-MRA, and to compare them between patients who recently developed ipsilateral symptomatic ischemia and those who did not. Methods Between 2012 and 2014, 505 patients underwent Q-MRA in our institution. Among these, 33 patients who had unilateral ICA occlusion with primary collateral pathway were identified, and grouped into asymptomatic patients, stable patients with chronic infarction, and symptomatic patients with acute/subacute infarction. Mean VFR (mVFR) in intracranial arteries was measured and compared between the patients’ groups. Kruskal-Wallis test was used for statistical analysis. Results Six patients were asymptomatic, fifteen with chronic infarction were stable, and twelve with acute/subacute infarction were symptomatic. The mVFR of ipsilateral middle cerebral artery in symptomatic patients was significantly lower than those in stable or asymptomatic patients (73.7±45.6 mL/min vs. 119.9±36.1 mL/min vs. 121.8±42.0 mL/min; P=0.04). Total sum of the mVFR of ipsilateral anterior, middle, and posterior cerebral arteries was significantly lower in symptomatic patients than those in other groups (229.3±51.3 mL/min vs. 282.0±68.6 mL/min vs. 314.0±44.4 mL/min; P=0.02). Conclusions Q-MRA could be helpful to demonstrate the difference in the degree of primary collateral flow in ICA occlusion between the patients with recent symptomatic ischemia and those without.