Safety Review and Perspectives of Transcranial Focused Ultrasound Brain Stimulation

Lee Wonhye,Weisholtz Daniel S.,Strangman Gary E.,Yoo Seung-Schik 대한뇌신경재활학회 2021 뇌신경재활 Vol.14 No.1

Ultrasound is an important theragnostic modality in modern medicine. Technical advancement of both acoustic focusing and transcranial delivery have enabled administration of ultrasound waves to localized brain areas with few millimeters of spatial specificity and penetration depth sufficient to reach the thalamus. Transcranial focused ultrasound (tFUS) given at a low acoustic intensity has been shown to increase or suppress the excitability of region-specific brain areas. The neuromodulatory effects can outlast the sonication, suggesting the possibility of inducing neural plasticity needed for neurorehabilitation. Increasing numbers of studies have shown the efficacy and excellent safety profile of the technique, yet comparisons among the safety-related parameters have not been compiled. This review aims to provide safety information and perspectives of tFUS brain stimulation. First, the acoustic parameters most relevant to thermal/mechanical tissue damage are discussed along with regulated parameters for existing ultrasound therapies/diagnostic imaging. Subsequently, the parameters used in studies of large animals, non-human primates, and humans are surveyed and summarized in terms of the acoustic intensity and the mechanical index. The pulse-mode operation and the use of low ultrasound frequency for tFUS-mediated brain stimulation warrant the establishment of new safety guidelines/recommendations for the use of the technique among healthy volunteers, with additional cautionary requirements for its clinical translation.

Tissue Reconstruction: Cellular Hydrogel Biopaper for Patterned 3D Cell Culture and Modular Tissue Reconstruction (Adv. Healthcare Mater. 5/2012)

Lee, Wonhye,Bae, Chae Yun,Kwon, Seyong,Son, Jaejung,Kim, Jinho,Jeong, Yong,Yoo, Seung-Schik,Park, Je-Kyun Wiley (John WileySons) 2012 Advanced healthcare materials Vol.1 No.5

BioSubroutine: an Open Web Server for Bioinformatics Algorithms and Subroutines

Lee, Joowon,Kim, Hana,Lee, Wonhye,Chung, Dongil,Bhak, Jong Korea Genome Organization 2005 Genomics & informatics Vol.3 No.1

We present BioSubroutine, an open depository server that automatically categorizes various subroutines frequently used in bioinformatics research. We processed a large bioinformatics subroutine library called Bio.pl that was the first Bioperl subroutine library built in 1995. Over 1000 subroutines were processed automatically and an HTML interface has been created. BioSubroutine can accept new subroutines and algorithms from any such subroutine library, as well as provide interactive user forms. The subroutines are stored in an SQL database for quick searching and accessing. BioSubroutine is an open access project under the BioLicense license scheme.

비자의 입원에 관련된 주요 요인에 대한 입원적합성심사 위원들의 의견 분석

이원선(Won Sun Lee),심아림(Ah Rim Sim),이원혜(Wonhye Lee),전진용(Jin Yong Jun),박동연(Dong Yeon Park),황태연(Tae-Yeon Hwang) 대한사회정신의학회 2023 사회정신의학 Vol.28 No.2

목적 : 2016년 개정된 정신건강복지법에 따라, 정신과적 비자의 입원 적합성 심사를 위해 입원적합성심사 위원회(이하 입적심)가 2018년 6월부터 운영되었다. 입적심 제도의 검토와 보완을 위해 비자의 입원 심사 현황을 파악하고자 입적심 위원들의 심사기준, 주요 쟁점 사안 및 입적심 운영에 대한 의견을 조사하였다. 방법 : 2020년 6월부터 7월까지 국립정신건강센터 입적심 위원들을 대상으로 설문지를 배포하였고 총 74명의 설문지가 수거되었다. 설문지에는 비자의 입원의 적합성에 대한 주요 심사사항, 심사기준 및 위원회 운영에 관련된 내용들이 포함되었고, 세부질문으로 구성된 4개 영역의 선택형 문항과 서술형 문항으로 구성되었다. 조사 내용에 대한 기술적 분석에 추가하여 설문 문항에 대한 연령, 나이, 직역, 소위별 응답의 차이를 카이제곱 검정으로 분석하였다. 결과 :입원 적합성 심사 시 고려 사항의 우선순위는 ‘자·타해 위험성’(81.1%), ‘입원 필요성’(56.8%), ‘이송 강압성’(54.1%) 순이었으며, 이송 시 강압성에 대해서는 ‘신체 강박’(83.8%), ‘이송침대에 강박’(68.9%), ‘강압적 분위기’(32.4%)를 우선적으로 고려하는 것으로 나타났다. 설문 항목에 대한 참여자의 사회 인구학적 인자를 분석한 결과, 전반적인 심사 견해에 있어서는 사회 인구학적인자와 유의미한 연관성은 두드러지지 않았으나, 알코올, 청소년 문제와 같은 특수 상황에 대한 심사에는 직군별 차이를 보였다. 아울러 위원들은 자·타해 위험성에 대한 세부 기준 및 위원별 심사 기준의 통일성을 높이기 위한 방안 마련을 제안하는 것으로 나타났다. 결론 : 본 연구를 통하여 입적심 위원들의 심사 견해에 대한 국내 수도권 지역 자료를 확보하고 분석할 수 있었다. 이를 바탕으로 입적심 운영 및 제도를 보완하고 개선한다면 공정하고 일관된 비자의 입원 심사가 이루어질 것으로 기대한다. Objectives: In accordance with the revised Mental Health and Welfare Act of June 2016, the Involuntary Admission Review Committee (hereinafter referred to as “the committee”) has been established since June 2018 to assess the suitability of involuntary admission of psychiatric patients. To examine and improve the committee system, this study surveyed the assessment criteria, major issues, and opinions on the operation of the committee, with a focus on the assessment of involuntary hospitalization. Methods: From June to July 2020, a survey was distributed to 74 members of the National Center for Mental Health's committee for the assessment of involuntary hospitalization. The survey consisted of multiple-choice and open-ended questions regarding the major assessment criteria, standards, and operation of the committee in relation to the suitability of involuntary admission. The survey data were analyzed using chi-square tests to examine differences in responses based on age, job position, and other demographic variables. Results: The prioritized considerations in assessing the suitability of involuntary admission were ‘risk for suicidality/homicidality’ (81.1%), ‘necessity of hospitalization’ (56.8%), and ‘coercive transport’ (54.1%). Regarding the use of coercion during transport, ‘physically coercion’ (83.8%), ‘restraint on a stretcher car’ (68.9%), and ‘coercive atmosphere’ (32.4%) were the most commonly considered factors. While there was no significant association between demographic variables and overall assessment opinions, differences were observed in the assessment of special situations such as alcohol use and adolescent issues based on job position. The committee members suggested measures to increase uniformity in assessment standards for the risk of harm to oneself or others and individual assessment standards. Conclusion: This study provides the domestic data on the assessment opinions of committee members for involuntary hospitalization. Based on these findings, we expect that fair and consistent assessment of involuntary admission of psychiatric patients can be achieved through improvements and revisions in the committee system and operation.

Cortical Volumetric Correlates of Childhood Trauma, Anxiety, and Impulsivity in Bipolar Disorder

Song Hyehyun,Chon Myong-Wuk,Ryu Vin,Yu Rina,Lee Dong-Kyun,Lee Hyeongrae,Lee Wonhye,Lee Jung Hyun,Park Dong Yeon 대한신경정신의학회 2020 PSYCHIATRY INVESTIGATION Vol.17 No.7

Objective More recently, attention has turned to the linkage between childhood trauma and emotional dysregulation, but the evidence in bipolar disorder (BD) is limited. To determine neurobiological relationships between childhood trauma, current anxiety, and impulsivity, we investigated cortical volumetric correlates of these clinical factors in BD.Methods We studied 36 patients with DSM-5 BD and 29 healthy controls. Childhood trauma, coexisting anxiety, and impulsivity were evaluated with the Korean version-Childhood Trauma Questionnaire (CTQ), the Korean version-Beck Anxiety Inventory (BAI), and the Korean version-Barratt Impulsiveness Scale (BIS). Voxel-based morphometry (VBM) was used to assess gray matter volume (GMV) alterations on the brain magnetic resonance imaging (MRI). Partial correlation analyses were conducted to examine associations between the GMV and each scale in the BD group.Results Childhood trauma, anxiety, and impulsivity were interrelated in BD. BD patients revealed significant inverse correlations between the GMV in the right precentral gyrus and CTQ scores (r=-0.609, p<0.0003); between the GMV in the left middle frontal gyrus and BAI scores (r=-0.363, p=0.044). Moreover, patients showed similar tendency of negative correlations between the GMV in the right precentral gyrus and BIS scores; between the GMV in the left middle frontal gyrus and CTQ scores.Conclusion The present study provides evidence for a neural basis between childhood trauma and affect regulations in BD. The GMV alterations in multiple frontal lobe areas may represent neurobiological markers for anticipating the course of BD.

국내 정신건강의학과 의사의 전자 소통, 소셜 미디어 사용 현황과 지침 개발을 위한 예비연구

조민호(Minho Jo),이원혜(Wonhye Lee),황태연(Tae-Yeon Hwang) 대한사회정신의학회 2020 사회정신의학 Vol.25 No.1

목 적 : 소셜 미디어 등 웹서비스의 사용이 증가하며 임상 현장에서 의사-환자 관계에도 영향을 끼치고 있다. 이러한 상황에서 정신건강 의학과 의사들의 환자와의 전자 소통, 소셜 미디어 사용 현황을 알아보고 의료 정보의 제공과 소통의 기회를 확대하고 부작용을 최소화하기 위한 올바른 소셜 미디어의 사용에 관한 가이드라인 개발을 위하여 조사를 진행했다. 방 법 : 정신건강의학과 의사를 대상으로 설문지를 배포하였고 총 243명의 설문지가 수거됐다. 설문지에는 환자나 타인과 이메일 또는 문자 메시지 소통, 소셜 미디어 사용 및 개인정보 접근 제한 등과 환자와의 온라인 소통에 대한 가이드라인의 필요성 등이 포함됐다. 설문지 문항에 대한 기술통계분석과 연령별, 경력별, 근무지 형태별 차이를 분석했다. 결 과 : 응답자의 31.3%가 환자와 이메일로 소통하였고 이 중 5.3%만이 서면 동의를 받았다. 환자와 문자 메시지로 소통한다는 응답자는 39.1%였다. 반면 환자로부터는 이메일 소통 요청을 45.7%가 받고 있었다. 응답자의 26.7%는 환자의 사적인 정보를 인터넷으로 검색 하고 있었고 온라인 포스팅을 하고 있는 응답자는 51.0%였으나 20.2%는 개인정보 접근 제한을 전혀 하지 않았다. 개인정보 접근 제한은 연령대별로 차이가 있었다. 응답자의 83.5%가 학회나 협회 차원의 전자 소통, 소셜 네트워킹 등 온라인 상 환자와의 소통에 관한 가이드라인이 필요하다고 응답했다. 결 론 : 본 연구를 통하여 정신건강의학과 의사들이 임상현장에서 환자와 많은 전자 소통이나 소셜 미디어 사용을 하지 않고 있으나, 환자들의 소통 욕구는 증가하고 있었고, 개인정보 보호와 비밀 유지, 정확한 의료 정보교환 등을 위해 향후 가이드라인을 개발하고 준수할 필요성이 있음을 알 수 있었다. Objectives : The use of social media and other web services is increasing, and it is affecting doctor-patient relationships at the clinical situation. Under these circumstances, this research was conducted to investigate the Korean psychiatrists’ usage of social media, electronic communication with patients and colleagues and to develop guidelines to prevent possible negative effects. Methods : The questionnaire included e-mail or text messaging with patients or others, social media usage and privacy restrictions, and the need for guidelines for online communication with patients. The questionnaire was distributed through on-off line to psychiatrists and a total of 243 replies questionnaires were collected. Descriptive statistical analysis was conducted on the questions and additionally, non-parametric tests were conducted to analyze differences in age, career, and type of work for questionnaire questions. Results : 31.3% of the respondents communicated with patients via e-mail, and only 5.3 percent of them received written con-sent. 39.1% of the respondents reported that they communicate with patients via text messages. 26.7% of the them were searching for patients' personal information on the Internet. Before psychiatric interview, while 51.0% of respondents were posting online, 20.5% did not restrict access to personal information at all. Restrictions on personal information ac-cess differed by age group. 83.5% of the respondents reported that they need guidelines on online communication with patients. Conclusion : This study shows that psychiatrists in Korea are not so much using email and social media while they are communicating with their patients in the clinical setting even though they are observing the patients’ demands are increasing. Many psychiatrists agreed to develop and follow the guideline for the electronic communication and social media usage with patients and colleagues, which include privacy and personal data protection, medical information provision and transfer.

Transcranial Focused Ultrasound to the Thalamus Is Associated with Reduced Extracellular GABA Levels in Rats

Yang, Po Song,Kim, Hyungmin,Lee, Wonhye,Bohlke, Mark,Park, Shinsuk,Maher, Timothy J.,Yoo, Seung-Schik S. Karger AG 2012 Neuropsychobiology Vol.65 No.3

<P>Abstract</P><P><I>Objective:</I> Transcranial focused ultrasound (FUS), with its ability to non-invasively modulate the excitability of region-specific brain areas, is gaining attention as a potential neurotherapeutic modality. The aim of this study was to examine whether or not FUS administered to the brain could alter the extracellular levels of glutamate and γ-aminobutyric acid (GABA), which are representative excitatory and inhibitory amino acid neurotransmitters, respectively. <I>Methods:</I> FUS, delivered in the form of a train of pulses, was applied to the thalamus of Sprague-Dawley rats transcranially. Glutamate and GABA were directly sampled from the frontal lobe of the rat brain via a direct microdialysis technique before, during, and after the sonication. The dialysate concentrations were determined by high-performance liquid chromatography. <I>Results:</I> The individual levels of the neurotransmitters sampled were normalized to the baseline level for each rat. In terms of the changes in extracellular glutamate levels, there was no difference between the FUS-treated group and the unsonicated control group. However, extracellular GABA levels started to decrease upon sonication and remained reduced (approximately 20% below baseline; repeated-measures ANOVA, p < 0.05, adjusted for multiple comparisons) compared to the control group. <I>Conclusion:</I> The ability to modulate region-specific brain activity, along with the present evidence of the ability to modulate neurotransmission, demonstrates the potential utility of FUS as a completely new non-invasive therapeutic modality.</P><P>Copyright © 2012 S. Karger AG, Basel</P>

Suppression of EEG visual-evoked potentials in rats through neuromodulatory focused ultrasound

Kim, Hyungmin,Park, Michael Y.,Lee, Stephanie D.,Lee, Wonhye,Chiu, Alan,Yoo, Seung-Schik Wolters Kluwer Health | Lippincott Williams Wilkin 2015 NEUROREPORT - Vol.26 No.4

We investigated the use of pulsed low-intensity focused ultrasound (FUS) to suppress the visual neural response induced by light stimulation in rodents. FUS was administered transcranially to the rat visual cortex using different acoustic intensities and pulsing duty cycles. The visual-evoked potentials (VEPs) generated by an external strobe light stimulation were measured three times before, once during, and five times after the sonication. The VEP magnitude was suppressed during the sonication using a 5% duty cycle (pulse-repetition frequency of 100 Hz) and a spatial-peak pulse-average acoustic intensity of 3 W/cm; however, this suppressive effect was not present when a lower acoustic intensity and duty cycle were used. The application of a higher intensity and duty cycle resulted in a slight elevation in VEP magnitude, which suggested excitatory neuromodulation. Our findings demonstrate that the application of pulsed FUS to the region-specific brain area not only suppresses its excitability, but can also enhance the excitability depending on the acoustic intensity and the rate of energy deposition. This bimodal feature of FUS-mediated neuromodulation, which has been predicted by numerical models on neural membrane capacitance change by the external acoustic pressure waves, suggests its versatility for neurotherapeutic applications.

A pilot clinical study of low-intensity transcranial focused ultrasound in Alzheimer’s disease

정현석,Im Jooyeon Jamie,Park Jong-Sik,Na Seunghee,Lee Wonhye,Yoo Seung-Schik,송인욱,Chung Yong-An 대한초음파의학회 2021 ULTRASONOGRAPHY Vol.40 No.4

Purpose: Increasing attention has been paid to low-intensity transcranial focused ultrasound (tFUS) for its potential therapeutic effects in Alzheimer's disease (AD). While preclinical studies have shown promising therapeutic effects of low-intensity tFUS in AD models, its efficacy and safety remain unclear in humans. In this pilot study, we investigated the effects of low-intensity tFUS on blood-brain barrier opening, the regional cerebral metabolic rate of glucose (rCMRglu), and cognition in patients with AD. Methods: After receiving institutional review board approval, four patients with AD received tFUS to the hippocampus immediately after an intravenous injection of a microbubble ultrasound contrast agent. Sonication was delivered at low-intensity, at a pressure level below the threshold for blood-brain barrier opening. Patients underwent brain magnetic resonance imaging, 18F-fluoro-2-deoxyglucose positron emission tomography, and neuropsychological assessments before and after the tFUS procedure. A whole-brain voxel-wise paired t test was conducted to compare rCMRglu before and after tFUS. Results: The sonication, as anticipated, did not show evidence of active blood-brain barrier opening on T1 dynamic contrast-enhanced magnetic resonance imaging. rCMRglu in the superior frontal gyrus (P<0.001), middle cingulate gyrus (P<0.001), and fusiform gyrus increased after tFUS (P=0.001). Patients demonstrated mild improvement in measures of memory, executive, and global cognitive function following tFUS. No adverse events were reported. Conclusion: These results suggest that hippocampal sonication with low-intensity tFUS may have beneficial effects on cerebral glucose metabolism and cognitive function in patients with AD. Further larger studies are needed to confirm the therapeutic efficacy of tFUS in AD. Purpose: Increasing attention has been paid to low-intensity transcranial focused ultrasound (tFUS) for its potential therapeutic effects in Alzheimer's disease (AD). While preclinical studies have shown promising therapeutic effects of low-intensity tFUS in AD models, its efficacy and safety remain unclear in humans. In this pilot study, we investigated the effects of low-intensity tFUS on blood-brain barrier opening, the regional cerebral metabolic rate of glucose (rCMRglu), and cognition in patients with AD.Methods: After receiving institutional review board approval, four patients with AD received tFUS to the hippocampus immediately after an intravenous injection of a microbubble ultrasound contrast agent. Sonication was delivered at low-intensity, at a pressure level below the threshold for blood-brain barrier opening. Patients underwent brain magnetic resonance imaging, 18F-fluoro-2-deoxyglucose positron emission tomography, and neuropsychological assessments before and after the tFUS procedure. A whole-brain voxel-wise paired t test was conducted to compare rCMRglu before and after tFUS.Results: The sonication, as anticipated, did not show evidence of active blood-brain barrier opening on T1 dynamic contrast-enhanced magnetic resonance imaging. rCMRglu in the superior frontal gyrus (P<0.001), middle cingulate gyrus (P<0.001), and fusiform gyrus increased after tFUS (P=0.001). Patients demonstrated mild improvement in measures of memory, executive, and global cognitive function following tFUS. No adverse events were reported.Conclusion: These results suggest that hippocampal sonication with low-intensity tFUS may have beneficial effects on cerebral glucose metabolism and cognitive function in patients with AD. Further larger studies are needed to confirm the therapeutic efficacy of tFUS in AD.

양극성 장애 환자에서 불안이 질병 경과에 미치는 영향 : 전향적 추적관찰에 대한 중간분석

김수정,김소정,송혜현,이원혜,전명욱,남윤영,박동연,Kim, Soojeong,Kim, So Jeong,Song, Hye Hyun,Lee, Wonhye,Chon, Myong-Wuk,Nam, Yoon Young,Park, Dong Yeon 대한생물정신의학회 2021 생물정신의학 Vol.28 No.1

Objectives Despite growing attention to anxiety in bipolar disorder (BD), little research has assessed anxiety symptoms in the course of BD. The current prospective follow-up study examines the influence of subjectively and objectively measured anxiety symptoms on the course of BD. Methods A total of 49 patients with BD were followed-up prospectively for average of one year at an average of four months interval. The Korean version of the Beck Anxiety Inventory (K-BAI), the Hamilton Anxiety Rating Scale, heart rate variability (HRV) were used to measure anxiety subjectively, objectively and physiologically. Participants were divided into high and low anxiety groups based on their K-BAI scores. Kaplan-Meier survival analysis was performed to compare the recurrence of mood episode, suicide attempt, emergency room visit, and psychiatric hospitalization between two groups. Mediators were investigated with Cox proportional hazards models. Results Compared to the low anxiety group, the high anxiety group reported significantly higher impulsiveness (p = 0.016) and lower high frequency component on HRV (p = 0.007) after controlling for severity of BD. Regarding survival analysis, the high anxiety group showed hastened depressive episode recurrence (p = 0.048) and suicidal ideation was the mediator of the hazard ratio (HR) 1.089 (p = 0.029) in the Cox model. Moreover, the high anxiety group showed a tendency of accelerated suicide attempt (p = 0.12) and impulsivity was the risk factor of suicide attempt (HR = 1.089, p = 0.036). Conclusions This interim analysis of prospective study suggests that high anxiety level in BD may anticipate unfavorable course. Further studies are needed to understand the multifactorial mechanism of anxious bipolar patients.