Quantitative Feasibility Evaluation of ¹¹C-Methionine Positron Emission Tomography Images in Gamma Knife Radiosurgery : Phantom-Based Study and Clinical Application

Lim, Sa-Hoe,Jung, Tae-Young,Jung, Shin,Kim, In-Young,Moon, Kyung-Sub,Kwon, Seong-Young,Jang, Woo-Youl The Korean Neurosurgical Society 2019 Journal of Korean neurosurgical society Vol.62 No.4

Objective : The functional information of $^{11}C$-methionine positron emission tomography (MET-PET) images can be applied for Gamma knife radiosurgery (GKR) and its image quality may affect defining the tumor. This study conducted the phantom-based evaluation for geometric accuracy and functional characteristic of diagnostic MET-PET image co-registered with stereotactic image in Leksell $GammaPlan^{(R)}$ (LGP) and also investigated clinical application of these images in metastatic brain tumors. Methods : Two types of cylindrical acrylic phantoms fabricated in-house were used for this study : the phantom with an array-shaped axial rod insert and the phantom with different sized tube indicators. The phantoms were mounted on the stereotactic frame and scanned using computed tomography (CT), magnetic resonance imaging (MRI), and PET system. Three-dimensional coordinate values on co-registered MET-PET images were compared with those on stereotactic CT image in LGP. MET uptake values of different sized indicators inside phantom were evaluated. We also evaluated the CT and MRI co-registered stereotactic MET-PET images with MR-enhancing volume and PET-metabolic tumor volume (MTV) in 14 metastatic brain tumors. Results : Imaging distortion of MET-PET was maintained stable at less than approximately 3% on mean value. There was no statistical difference in the geometric accuracy according to co-registered reference stereotactic images. In functional characteristic study for MET-PET image, the indicator on the lateral side of the phantom exhibited higher uptake than that on the medial side. This effect decreased as the size of the object increased. In 14 metastatic tumors, the median matching percentage between MR-enhancing volume and PET-MTV was 36.8% on PET/MR fusion images and 39.9% on PET/CT fusion images. Conclusion : The geometric accuracy of the diagnostic MET-PET co-registered with stereotactic MR in LGP is acceptable on phantom-based study. However, the MET-PET images could the limitations in providing exact stereotactic information in clinical study.

Leksell Frame-Based Stereotactic Biopsy for Infratentorial Tumor : Practical Tips and Considerations

Tae-Kyu Lee,Sa-Hoe Lim,Jangshik Jeong,Su Jee Park,Yeong Jin Kim,Kyung-Sub Moon,In-Young Kim,Shin Jung,Tae-Young Jung 대한신경외과학회 2024 Journal of Korean neurosurgical society Vol.67 No.2

The Leksell frame-based transcerebellar approach was proposed with the arc support frame attached upside down to the Z coordinate. This study presented practical tips and considerations for obtaining adequate tissue samples for deep-seated cerebellar lesions or lower brainstem lesions specifically those accessible via the cerebellar peduncle. For practical insights, the Leksell coordinate frame G was fixed to prevent the anterior screw implantation within the temporalis muscle, to avoid interference with the magnetic resonance (MR)-adapter, and taking into account the magnetic field of MR in close proximity to the tentorium. After mounting of indicator box, the MR imaging evaluation should cover both the indicator box and the infratentorial region that deviated from it. The coordinates [X, Y, Za, Arc0, Ringa0] obtained from Leksell SurgiPlan® software (Elekta, Stockholm, Sweden) with arc 00 located on the patient’s right side were converted to [X, Y, Zb=360–Za, Arc0, Ringb0=Ringa0–1800]. The operation was performed in the prone position under general anesthesia in four patients with deep cerebellar (n=3) and brainstem (n=1) tumors. The biopsy results showed two cases of diffuse large B-cell lymphoma, one metastatic braintumor and one glioblastoma. One patient required frame repositioning as a complication. Drawing upon the methodology outlined in existing literature, we anticipate that imparting supplementary expertise could render the stereotactic biopsy of infratentorial tumors more consistent and manageable for the practitioner, thereby facilitating adequate tissue samples and minimizing patient complications.

The Tumor Control According to Radiation Dose of Gamma Knife Radiosurgery for Small and Medium-Sized Brain Metastases from Non-Small Cell Lung Cancer

Park, Sue Jee,Lim, Sa-Hoe,Kim, Young-Jin,Moon, Kyung-Sub,Kim, In-Young,Jung, Shin,Kim, Seul-Kee,Oh, In-Jae,Hong, Jong-Hwan,Jung, Tae-Young The Korean Neurosurgical Society 2021 Journal of Korean neurosurgical society Vol.64 No.6

Objective : The effectiveness of gamma knife radiosurgery (GKR) in the treatment of brain metastases is well established. The aim of this study was to evaluate the efficacy and safety of maximizing the radiation dose in GKR and the factors influencing tumor control in cases of small and medium-sized brain metastases from non-small cell lung cancer (NSCLC). Methods : We analyzed 230 metastatic brain tumors less than 5 mL in volume in 146 patients with NSCLC who underwent GKR. The patients had no previous radiation therapy for brain metastases. The pathologies of the tumors were adenocarcinoma (n=207), squamous cell carcinoma (n=18), and others (n=5). The radiation doses were classified as 18, 20, 22, and 24 Gy, and based on the tumor volume, the tumors were categorized as follows : small-sized (less than 1 mL) and medium-sized (1-3 and 3-5 mL). The progression-free survival (PFS) of the individual 230 tumors and 146 brain metastases was evaluated after GKR depending on the pathology, Eastern Cooperative Oncology Group (ECOG) performance score (PS), tumor volume, radiation dose, and anti-cancer regimens. The radiotoxicity after GKR was also evaluated. Results : After GKR, the restricted mean PFS of individual 230 tumors at 24 months was 15.6 months (14.0-17.1). In small-sized tumors, as the dose of radiation increased, the tumor control rates tended to increase (p=0.072). In medium-sized tumors, there was no statistically difference in PFS with an increase of radiation dose (p=0.783). On univariate analyses, a statistically significant increase in PFS was associated with adenocarcinomas (p=0.001), tumors with ECOG PS 0 (p=0.005), small-sized tumors (p=0.003), radiation dose of 24 Gy (p=0.014), synchronous lesions (p=0.002), and targeted therapy (p=0.004). On multivariate analyses, an improved PFS was seen with targeted therapy (hazard ratio, 0.356; 95% confidence interval, 0.150-0.842; p=0.019). After GKR, the restricted mean PFS of brain at 24 months was 9.8 months (8.5-11.1) in 146 patients, and the pattern of recurrence was mostly distant within the brain (66.4%). The small and medium-sized tumors treated with GKR showed radiotoxicitiy in five out of 230 tumors (2.2%), which were controlled with medical treatment. Conclusion : The small-sized tumors were effectively controlled without symptomatic radiation necrosis as the radiation dose was increased up to 24 Gy. The medium-sized tumors showed potential for symptomatic radiation necrosis without signifcant tumor control rate, when greater than 18 Gy. GKR combined targeted therapy improved the tumor control of GKR-treated tumors.

Development of On-Line Health Monitoring System for Pipes in Nuclear Power Plants

Eom, Heung Seop,Lim, Sa Hoe,Kim, Jae Hee,Kim, Young H.,Kim, Hak Joon,Song, Sung Jin Trans Tech Publications, Ltd. 2006 Key Engineering Materials Vol.321 No.-

<P>This study was aimed at developing an effective method and a system for on-line health monitoring of pipes in nuclear power plants by using ultrasonic guided waves. For this purpose we developed a multi-channel ultrasonic guided wave system for a long-range inspection of pipes and a few techniques which can effectively find defects in pipes. To validate the developed system we performed a series of experiments and analyzed the results.</P>

한국표준형 원전 증기발생기 Stay 용접부 자동검사시스템 및 현장 검증

임사회,박치승,박철훈,주금종,노희충,윤광식,Lim, Sa Hoe,Park, Chi Seung,Park, Chul Hoon,Joo, Keum Chong,Noh, Hee Chung,Yoon, Kwang Sik 한국압력기기공학회 2010 한국압력기기공학회 논문집 Vol.6 No.1

The stay cylinder weld at the steam generator of Korean Standard Nuclear Power Plants is safety class I component and is subjected to be inspected by the volumetric examination such as ultrasonic method. As accessibility of this area is limited due to the narrow space and high radiation, the existing manual inspection method involves various difficulties. Moreover operators may be exposed to internal contamination by contaminated dust during the surface buffing process to improve the inspection reliability of this area. Recently the new automatic inspection system for stay cylinder welds has been developed. The inspection system basically consists of a driving assembly, data acquisition device and signal processing units. The driving assembly is classified by 1) the scanner for inspecting and buffing the weld, 2) pillars for guiding the scanner and 3) the base frame for loading and supporting pillars. The scanner has 4 sensor modules to inspect in 4 refracted angles and 4 incident directions. These components can be inserted into the skirt of the stay cylinder through the manway hole and assembled easily by one-touch in the skirt. Data acquisition device and signal processing units developed in previous works are also newly upgraded for better processing of data analysis and evaluation. The system has been successfully demonstrated not only in the mock-up but also in the field. In this paper, newly developed inspection system for the stay cylinder weld of the steam generator is introduced and their field applications are discussed.

소듐냉각고속로 원자로 내부구조물의 소듐내부가시화를 위한 웨이브가이드 초음파센서의 적용 가능성 연구

주영상(Young-Sang Joo),임사회(Sa-Hoe Lim),박창규(Chang-Gyu Park),이재한(Jae-Han Lee) 한국비파괴검사학회 2008 한국비파괴검사학회지 Vol.28 No.4

Bacitracin Inhibits the Migration of U87-MG Glioma Cells via Interferences of the Integrin Outside-in Signaling Pathway

Li, Songyuan,Li, Chunhao,Ryu, Hyang-Hwa,Lim, Sa-Hoe,Jang, Woo-Youl,Jung, Shin The Korean Neurosurgical Society 2016 Journal of Korean neurosurgical society Vol.59 No.2

Objective : Protein disulfide isomerase (PDI) acts as a chaperone on the cell surface, and it has been reported that PDI is associated with the tumor cell migration and invasion. The aims of this study are to investigate the anti-migration effect of bacitracin, which is an inhibitor of PDI, and the associated factor in this process. Methods : U87-MG glioma cells were treated with bacitracin in 1.25, 2.5, 3.75, and 5.0 mM concentrations. Western blot with caspase-3 was applied to evaluate the cytotoxicity of bacitracin. Adhesion, morphology, migration assays, and organotypic brain-slice culture were performed to evaluate the effect of bacitracin to the tumor cell. Western blot, PCR, and gelatin zymography were performed to investigate the associated factors. Thirty glioma tissues were collected following immunohistochemistry and Western blot. Results : Bacitracin showed a cytotoxicity in 3rd (p<0.05) and 4th (p<0.001) days, in 5.0 Mm concentration. The cell adhesion significantly decreased and the cells became a round shape after treated with bacitracin. The migration ability, the expression of phosphorylated focal adhesion kinase (p-FAK) and matrix metalloproteinase-2 (MMP-2) decreased in a bacitracin dose- and time-dependent manner. The U87-MG cells exhibited low-invasiveness in the 2.5 mM, compared with the untreated in organotypic brain-slice culture. PDI was expressed in the tumor margin, and significantly increased with histological glioma grades (p<0.001). Conclusion : Bacitracin, as a functional inhibitor of PDI, decreased the phosphorylated FAK and the secreted MMP-2, which are the downstream of integrin and play a major role in cell migration and invasion, might become one of the feasible therapeutic strategies for glioblastoma.

Treatment Outcome of Gamma Knife Radiosurgery for Petroclival Meningiomas: Retrospective Analysis of a Single Institution Experience

( Myeong-hun Ha ),( Woo-youl Jang ),( Tae-young Jung ),( In-young Kim ),( Sa-hoe Lim ),( Kyung-sub Moon ),( Shin Jung ) 대한뇌종양학회 대한신경종양학회 2020 Brain Tumor Research and Treatment Vol.8 No.2

Background Although Gamma Knife radiosurgery (GKRS) has been widely used for intracranial meningiomas as an alternative or adjuvant treatment, guidelines have not been established for the selection of patients with petroclival meningioma (PCM) for GKRS. In this study, we reported the factors related to tumor progression and postoperative complications in PCM patients treated by GKRS, with a review of the literatures. Methods Between 2004 and 2019, 64 patients (52 patients for alternative and 12 patients for adjuvant treatment) with PCM underwent GKRS in our institution. The clinical and radiological factors were retrospectively analyzed. The mean radiologic follow-up duration was 58.4 months (range, 6-164 months). The mean tumor volume and diameter before GKRS were 13.4 cm³ and 2.9 cm, respectively. The median marginal dose was 12 Gy (range, 10-14 Gy) with a 50% median isodose line. Fractionation was used in 19 cases (29%, two fractionations in 5 cases & three fractionations in 14 cases). Results Progression was noted in 7 cases (10.9%) and the progression-free survival rates were 91.1% at 5 years and 69.6% at 10 years. Although large in volume, moderate to severe peritumoral edema and male gender were somewhat related to progression, they did not reach statistical significance. Ten patients (15.6%) developed complications after GKRS. The most common complication was cranial nerve deficit (n=8), followed by hemiparesis, cognitive dysfunction, and hydrocephalus. Large size (maximal diameter ≥5 cm) [hazard ratio (HR) 0.091, 95% confidence interval (CI) 0.014-0.608; p=0.013] and multiplicity (HR 0.102, 95% CI 0.018-0.573; p=0.009) were independent factors for developing complications after GKRS. Conclusion GKRS can be considered an effective and safe treatment for large-volume PCM. However, for patients with large size or multiple masses, the treatment method should be determined with caution because the probability of complications after GKRS may increase.

PDIA6 regulation of ADAM17 shedding activity and EGFR-mediated migration and invasion of glioblastoma cells

Kim, Tae-Wan,Ryu, Hyang-Hwa,Li, Song-Yuan,Li, Chun-Hao,Lim, Sa-Hoe,Jang, Woo-Youl,Jung, Shin American Association of Neurological Surgeons 2017 Journal of Neurosurgery Vol. No.

<B>OBJECTIVE</B><P>In patients with glioblastoma, local invasion of tumor cells causes recurrence and shortens survival. The goal of this study was to determine whether protein disulfide isomerase (PDI) A6 regulates migration and invasion of glioblastoma cells and the associated factors.</P><B>METHODS</B><P>U87MG cells were treated with either PDIA6 or ADAM17 small interfering RNA (siRNA) fragments or with both types of siRNA fragments, and expression was confirmed by reverse transcription-polymerase chain reaction and Western blot. Migration and invasion were assessed using a wound-healing assay, a Matrigel assay, and an organotypic culture system. After the U87MG cells were treated with siRNAs and epidermal growth factor receptor (EGFR) inhibitors, the expression of matrix metalloproteinase-2 (MMP-2), membrane Type 1-matrix metalloproteinase (MT1-MMP), integrin, phosphorylated focal adhesion kinase (pFAK), and phosphorylated EGFR (pEGFR) was detected by Western blotting and zymography.</P><B>RESULTS</B><P>U87MG cell migration and invasion increased significantly after inhibition of <I>PDIA6</I>. The MMP-2 activation ratio and ADAM17 activity (as a sheddase of the proligand) increased, and expression of pEGFR, pFAK, integrin α5β3, and MT1-MMP was induced, compared with control levels. Furthermore, heparin-binding epidermal growth factor (EGFR signaling ligand) was highly expressed in <I>PDIA6</I>-knockdown cells. After siPDIA6-transfected U87MG cells were treated with EGFR signaling inhibitors, expression of pFAK, MMP-2, and MT1-MMP decreased and invasion decreased significantly. Simultaneous double-knockdown of <I>PDIA6</I> and <I>ADAM17</I> reduced pEGFR and pFAK expression, compared with control levels.</P><B>CONCLUSIONS</B><P>The authors propose that inhibiting <I>PDIA6</I> could transduce EGFR signaling by activating and inducing <I>ADAM17</I> during migration and invasion of U87MG glioblastoma cells. The results of this study suggest that PDIA6 is an important component of EGFR-mediated migration and invasion of U87MG cells. This is the first report of the effects of PDIA6 on migration and invasion in glioblastoma.</P>

The Application of Magnetic Resonance Imaging-Deformed ¹¹C-Methionine-Positron Emission Tomography Images in Stereotactic Radiosurgery

Jung, Tae-Young,Jung, Shin,Ryu, Han-Seung,Kim, In-Young,Jang, Woo-Youl,Moon, Kyung-Sub,Lim, Sa-Hoe,Kim, Dong-Yeon,Kang, Sae-Ryung,Min, Jung-Joon,Bom, Hee-Seung,Kim, Seul-Kee,Kwon, Seong Young S. Karger AG 2019 Stereotactic and functional neurosurgery Vol.97 No.4

<P><B><I>Background:</I></B> Although ¹¹C-methionine positron emission tomography (MET-PET) images can be fused with magnetic resonance (MR) images using planning software for gamma knife radiosurgery (GKR), the stereotactic information has limited value in patients with recurrent malignant brain tumor due to the difference in imaging protocols between MET-PET and MR images. The aim of this study was to evaluate the clinical application of MR imaging (MRI)-deformed MET-PET images in GKR using a deformable registration tool. <B><I>Methods:</I></B> We examined the enhanced MR stereotactic images, MET-PET and MRI-deformed MET-PET images without stereotactic information for 12 newly developed metastatic brain tumors. MET-PET and MRI-deformed MET-PET images were co-registered with the MR stereotactic images using radiosurgery planning software. Visual analysis was performed to determine whether the MET-PET and MR images matched better after using the deformable registration tool. In addition, the matching volume between MR and MET-PET images was compared before and after applying this tool. The matching volume was calculated as the metabolic tumor volume on the MET-PET images, including the MR-enhanced volume. The matching percentage was calculated as the matching volume divided by the MR-enhanced volume, multiplied by 100. <B><I>Results:</I></B> Visual analysis revealed that the MRI-deformed MET-PET images provided the same axial plane as that of the MR images, with the same window level, enabling easy identification of the tumor with the radiosurgery planning software. The mean matching percentage of the MET-PET/MR fusion images was 61.1% (range 24.7-94.7) and that of the MRI-deformed MET-PET/MR fusion images was 63.4% (range 20.8-94.3). No significant difference was found in the matching percentage between the two types of fusion images (<I>p</I> = 0.754). <B><I>Conclusions:</I></B> The MRI-deformed MET-PET images enable utilization of the functional information when planning a treatment in GKR without significant volume change.</P>