Publications by authors named "Hsiu-Mei Wu"

129 Publications

The Irradiated Brain Volume Within 12 Gy Is a Predictor for Radiation-Induced Changes After Stereotactic Radiosurgery in Patients With Unruptured Cerebral Arteriovenous Malformations.

Int J Radiat Oncol Biol Phys 2021 Jul 21. Epub 2021 Jul 21.

Institute of Brain Science, National Yang-Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan; Departments of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; Departments of Critical Care Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address:

Purpose: Our purpose was to determine whether the coverage of brain parenchyma within the 12 Gy radiosurgical volume (V12) correlates with the development of radiation-induced changes (RICs) in patients with unruptured cerebral arteriovenous malformations (AVM) after undergoing stereotactic radiosurgery (SRS).

Methods And Materials: This study conducted regular follow-up examinations of 165 patients with unruptured AVMs who had previously undergone SRS. The RICs identified in T2-weighted magnetic resonance imaging (MRI) scans at any time point in the first 3 years after SRS were labeled "early RICs." The RICs identified in T2-weighted MRI scans at 5-year follow-up brain images were labeled "late RICs." Fully automated segmentation was used to analyze the MRI scans from these patients, whereupon the volume and proportion of brain parenchyma within the V12 was calculated. Logistic regression analysis was used to characterize the factors affecting the incidence of early and late RICs of any grade after SRS.

Results: The median duration of follow-up was 70 months (range, 36-222). Early RICs were identified in 124 of the 165 patients with the highest grades as followed: grade 1 (103 patients), grade 2 (19 patients), and grade 3 (2 patients). Only 103 patients had more than 5 years follow-up, and late RICs were identified in 70 of 103 patients. Seventeen of 70 patients with late RICs were symptomatic. The median volume and proportion of brain parenchyma within the V12 was 22.4 cm (range, 0.6-63.9) and 58.7% (range, 18.4-76.8). Univariate analysis revealed that AVM volume and the brain volume within the V12 were correlated with the incidence of both early and late RICs after SRS. Multivariable analysis revealed that only the brain volume within the V12 was significantly associated with the incidence of early and late RICs after SRS.

Conclusions: In patients with unruptured AVM, the volume of brain parenchyma within the V12 was an important factor associated with the incidence of early and late RICs after SRS. Before SRS, meticulous radiosurgical planning to reduce brain parenchyma coverage within the V12 could reduce the risk of complications.
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http://dx.doi.org/10.1016/j.ijrobp.2021.05.135DOI Listing
July 2021

Clinical and genetic characterization of hereditary spastic paraplegia type 3A in Taiwan.

Parkinsonism Relat Disord 2021 Jun 11;87:87-91. Epub 2021 May 11.

Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Neurology, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan; Brain Research Center, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan. Electronic address:

Aim: To investigate the clinical and genetic features of hereditary spastic paraplegia (HSP) type 3A (SPG3A) in Taiwan.

Methods: Mutational analysis of the ATL1 gene was performed for 274 unrelated Taiwanese HSP patients. The diagnosis of SPG3A was ascertained by the presence of a heterozygous pathogenic mutation in ATL1. The SPG3A patients received clinical, electrophysiological, and neuroimaging evaluations. Disease severity was assessed by using Spastic Paraplegia Rating Scale (SPRS) and disability score. Nineteen single nucleotide polymorphism (SNP) markers flanking ATL1 were genotyped for haplotype analysis of ATL1 p.R416C mutation.

Results: Eighteen SPG3A patients from 11 families were identified. They typically presented a pure form HSP phenotype with disease onset ranging from age 1-68 years. Five heterozygous ATL1 mutations were identified, including p.R239C, p.V253I, p.Y336H, p.P342R and p.R416C. ATL1 p.R416C was the most common mutation and presented in five SPG3A pedigrees. Haplotype analyses demonstrated a shared haplotype in the 12 individuals carrying a p.R416C allele.

Conclusion: SPG3A accounts for 4% (11 out of 274) of HSP in the Taiwanese cohort. Patents with the ATL1 p.R416C mutation in Taiwan may descend from a common ancestor. This study defines the clinical and genetic features of SPG3A in Taiwan and provides useful information for the diagnosis and management, especially in patients of Han Chinese descent.
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http://dx.doi.org/10.1016/j.parkreldis.2021.05.004DOI Listing
June 2021

Effects of stereotactic radiosurgery versus conventional radiotherapy on body mass index in patients with craniopharyngioma.

J Neurosurg Pediatr 2021 May 14:1-7. Epub 2021 May 14.

1Department of Neurosurgery, Neurological Institute.

Objective: Hypothalamic obesity is common among patients with craniopharyngioma. This study examined whether precise stereotactic radiosurgery reduces the risk of hypothalamic obesity in cases of craniopharyngioma with expected long-term survival.

Methods: This cohort study included 40 patients who had undergone Gamma Knife radiosurgery (GKRS; n = 22) or fractionated radiotherapy (FRT; n = 18) for residual or recurrent craniopharyngioma. Neurological presentations, tumor volume changes, and BMI values were meticulously reviewed. The median clinical follow-up durations were 9.7 years in the GKRS group and 10.8 years in the FRT group.

Results: The median ages at the time of GKRS and FRT were 9.0 years and 10.0 years, respectively. The median margin dose of GKRS was 12.0 Gy (range 10.0-16.0 Gy), whereas the median dose of FRT was 50.40 Gy (range 44.1-56.3 Gy). Prior to GKRS or FRT, the median BMI values were 20.5 kg/m2 in the GKRS cohort and 20.0 kg/m2 in the FRT cohort. The median BMIs after radiation therapy at final follow-up were 21.0 kg/m2 and 24.0 kg/m2 for the GKRS and FRT cohorts, respectively. In the FRT cohort, BMI curves rapidly increased beyond the 85th percentile of the upper limit of the general population. BMI curves in the GKRS cohort increased more gradually, and many of the patients merged into the normal growth curve after adolescence. However, the observed difference was not statistically significant (p = 0.409).

Conclusions: The study compared the two adjuvant radiation modalities most commonly used for recurrent and residual craniopharyngioma. The authors' results revealed that precise radiosurgery dose planning can mediate the subsequent increase in BMI. There is every indication that meticulous GKRS treatment is an effective approach to treating craniopharyngioma while also reducing the risk of hypothalamic obesity.
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http://dx.doi.org/10.3171/2020.12.PEDS20165DOI Listing
May 2021

Disrupted metabolic connectivity in dopaminergic and cholinergic networks at different stages of dementia from F-FDG PET brain persistent homology network.

Sci Rep 2021 Mar 8;11(1):5396. Epub 2021 Mar 8.

Department of Radiology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei, 11217, Taiwan.

Dementia is related to the cellular accumulation of β-amyloid plaques, tau aggregates, or α-synuclein aggregates, or to neurotransmitter deficiencies in the dopaminergic and cholinergic pathways. Cellular and neurochemical changes are both involved in dementia pathology. However, the role of dopaminergic and cholinergic networks in metabolic connectivity at different stages of dementia remains unclear. The altered network organisation of the human brain characteristic of many neuropsychiatric and neurodegenerative disorders can be detected using persistent homology network (PHN) analysis and algebraic topology. We used F-fluorodeoxyglucose positron emission tomography (F-FDG PET) imaging data to construct dopaminergic and cholinergic metabolism networks, and used PHN analysis to track the evolution of these networks in patients with different stages of dementia. The sums of the network distances revealed significant differences between the network connectivity evident in the Alzheimer's disease and mild cognitive impairment cohorts. A larger distance between brain regions can indicate poorer efficiency in the integration of information. PHN analysis revealed the structural properties of and changes in the dopaminergic and cholinergic metabolism networks in patients with different stages of dementia at a range of thresholds. This method was thus able to identify dysregulation of dopaminergic and cholinergic networks in the pathology of dementia.
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http://dx.doi.org/10.1038/s41598-021-84722-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940645PMC
March 2021

Cerebrospinal fluid diversion and outcomes for lung cancer patients with leptomeningeal carcinomatosis.

Acta Neurochir (Wien) 2021 Mar 1. Epub 2021 Mar 1.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Objective: To investigate the outcomes of cerebrospinal fluid (CSF) diversion in lung cancer patients with leptomeningeal carcinomatosis (LMC).

Methods: A retrospective review of consecutive lung cancer patients with LMC suffering from increased intracranial pressure (IICP) and hydrocephalus between February 2017 and February 2020. We evaluated the survival benefit of CSF diversion surgery and assessed the outcomes of treatments administered post-LMC in terms of overall survival and shunt-related complications.

Results: The study cohort included 50 patients (median age: 59 years). Ventricular peritoneal (VP) shunts were placed in 33 patients, and lumbar peritoneal (LP) shunts were placed in 7 patients. Programmable shunts were placed in 36 patients. Shunt adjustment was performed in 19 patients. Kaplan-Meier analysis revealed that shunt placement increased overall survival from 1.95 months to 6.21 months (p = 0.0012) and increased Karnofsky Performance Scores (KPS) from 60 to 70. Univariate analysis revealed no difference between VP or LP shunts in terms of survival. No differences in post-shunt systemic treatments (tyrosine kinase inhibitors (TKIs) or systemic treatments) were observed in overall survival. Shunt-related complications were noted in 7 patients, including shunt obstruction (n = 4), infection (n = 1), and over-drainage (n = 2).

Conclusion: CSF diversion (VP or LP shunt) appears to be an effective and safe treatment for lung cancer patients with LMC and hydrocephalus. Programmable shunts should be considered for complex cases, which commonly require pressure adjustments as the disease progresses.
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http://dx.doi.org/10.1007/s00701-021-04763-wDOI Listing
March 2021

Treatment of WHO Grade 2 Meningiomas With Stereotactic Radiosurgery: Identification of an Optimal Group for SRS Using RPA.

Int J Radiat Oncol Biol Phys 2021 Jul 3;110(3):804-814. Epub 2021 Feb 3.

Department of Neurologic Surgery, University of Virginia Health System, Charlottesville, Virginia.

Purpose: This study assesses a large multi-institutional database to present the outcomes of World Health Organization grade 2 meningiomas treated with stereotactic radiosurgery (SRS). We also compare the 3-year progression-free survival (PFS) to that reported in the Radiation Therapy Oncology Group 0539 phase 2 cooperative group meningioma trial.

Methods And Materials: From an international, multicenter group, data were collected for grade 2 meningioma patients treated with SRS for demonstrable tumor from 1994 to 2019. Statistical methods used included the Kaplan-Meier method, Cox proportional hazards analysis, and recursive partitioning analysis.

Results: Two hundred thirty-three patients treated at 12 institutions were included. Patients presented at a median age of 60 years (range, 13-90), and many had at least 2 prior resections (30%) or radiation therapy (22%). Forty-eight percent of patients had prior gross total resection. At SRS, the median treatment volume was 6.1 cm (0.1-97.6). A median 15 Gy (10-30) was delivered to a median percent isodose of 50 (30-80), most commonly in 1 fraction (95%). A model was developed using recursive partitioning analysis, with one point attributed to age >50 years, treatment volume >11.5 cm, and prior radiation therapy or multiple surgeries. The good-prognostic group (score, 0-1) had improved PFS (P < .005) and time to local failure (P < .005) relative to the poor-prognostic group (score, 2-3). Age >50 years (hazard ratio = 1.85 [95% confidence interval, 1.09-3.14]) and multiple prior surgeries (hazard ratio = 1.80 [1.09-2.99]) also portended reduced PFS in patients without prior radiation therapy. Two hundred eighteen of 233 patients in this study qualified for the high-risk group of Radiation Therapy Oncology Group 0539, and they demonstrated similar outcomes (3-year PFS: 53.9% vs 58.8%). The good-prognostic group of SRS patients demonstrated slightly improved outcomes (3-year PFS: 63.1% vs 58.8%).

Conclusions: SRS should be considered in carefully selected patients with atypical meningiomas. We suggest the use of our good-prognostic group to optimize patient selection, and we strongly encourage the initiation of a clinical trial to prospectively validate these outcomes.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.048DOI Listing
July 2021

Applying artificial intelligence to longitudinal imaging analysis of vestibular schwannoma following radiosurgery.

Sci Rep 2021 Feb 4;11(1):3106. Epub 2021 Feb 4.

Department of Radiology, Taipei Veteran General Hospital, Taipei, Taiwan.

Artificial intelligence (AI) has been applied with considerable success in the fields of radiology, pathology, and neurosurgery. It is expected that AI will soon be used to optimize strategies for the clinical management of patients based on intensive imaging follow-up. Our objective in this study was to establish an algorithm by which to automate the volumetric measurement of vestibular schwannoma (VS) using a series of parametric MR images following radiosurgery. Based on a sample of 861 consecutive patients who underwent Gamma Knife radiosurgery (GKRS) between 1993 and 2008, the proposed end-to-end deep-learning scheme with automated pre-processing pipeline was applied to a series of 1290 MR examinations (T1W+C, and T2W parametric MR images). All of which were performed under consistent imaging acquisition protocols. The relative volume difference (RVD) between AI-based volumetric measurements and clinical measurements performed by expert radiologists were + 1.74%, - 0.31%, - 0.44%, - 0.19%, - 0.01%, and + 0.26% at each follow-up time point, regardless of the state of the tumor (progressed, pseudo-progressed, or regressed). This study outlines an approach to the evaluation of treatment responses via novel volumetric measurement algorithm, and can be used longitudinally following GKRS for VS. The proposed deep learning AI scheme is applicable to longitudinal follow-up assessments following a variety of therapeutic interventions.
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http://dx.doi.org/10.1038/s41598-021-82665-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862268PMC
February 2021

Stereotactic Radiosurgery for Atypical (World Health Organization II) and Anaplastic (World Health Organization III) Meningiomas: Results From a Multicenter, International Cohort Study.

Neurosurgery 2021 04;88(5):980-988

Department of Neurologic Surgery, Mayfield Clinic, Cincinnati, Ohio.

Background: Atypical and anaplastic meningiomas have reduced progression-free/overall survival (PFS/OS) compared to benign meningiomas. Stereotactic radiosurgery (SRS) for atypical meningiomas (AMs) and anaplastic meningiomas (malignant meningiomas, MMs) has not been adequately described.

Objective: To define clinical/radiographic outcomes for patients undergoing SRS for AM/MMs.

Methods: An international, multicenter, retrospective cohort study was performed to define clinical/imaging outcomes for patients receiving SRS for AM/MMs. Tumor progression was assessed with response assessment in neuro-oncology (RANO) criteria. Factors associated with PFS/OS were assessed using Kaplan-Meier analysis and a Cox proportional hazards model.

Results: A total of 271 patients received SRS for AMs (n = 233, 85.9%) or MMs (n = 38, 14.0%). Single-fraction SRS was most commonly employed (n = 264, 97.4%) with a mean target dose of 14.8 Gy. SRS was used as adjuvant treatment (n = 85, 31.4%), salvage therapy (n = 182, 67.2%), or primary therapy (1.5%). The 5-yr PFS/OS rate was 33.6% and 77.0%, respectively. Increasing age (hazard ratio (HR) = 1.01, P < .05) and a Ki-67 index > 15% (HR = 1.66, P < .03) negatively correlated with PFS. MMs (HR = 3.21, P < .05), increased age (HR = 1.04, P = .04), and reduced KPS (HR = 0.95, P = .04) were associated with shortened OS. Adjuvant versus salvage SRS did not impact PFS/OS. A shortened interval between surgery and SRS improved PFS for AMs (HR = 0.99, P = .02) on subgroup analysis. Radiation necrosis occurred in 34 (12.5%) patients. Five-year rates of repeat surgery/radiation were 33.8% and 60.4%, respectively.

Conclusion: AM/MMs remain challenging tumors to treat. Elevated proliferative indices are associated with tumor recurrence, while MMs have worse survival. SRS can control AM/MMs in the short term, but the 5-yr PFS rates are low, underscoring the need for improved treatment options for these patients.
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http://dx.doi.org/10.1093/neuros/nyaa553DOI Listing
April 2021

Stagnant venous outflow in ruptured arteriovenous malformations revealed by delayed quantitative digital subtraction angiography.

Eur J Radiol 2021 Jan 1;134:109455. Epub 2020 Dec 1.

School of Medicine, National Yang Ming University, Taipei, Taiwan; Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address:

Purpose: To investigate the reproducibility of quantitative digital subtraction angiography (QDSA) measurements and their associations with brain arteriovenous malformation (BAVM) hemorrhage.

Methods: From 2011-2019, 37 patients with BAVMs who had undergone both diagnostic and stereotactic DSA were divided into hemorrhagic and nonhemorrhagic groups. QDSA analysis was performed on the 2 DSA exams. The inter-exam reliabilities of QDSA measurements across the diagnostic and stereotactic DSA were tested using intraclass correlation coefficients (ICCs). Demographics, BAVM characteristics, and QDSA results for the hemorrhagic and nonhemorrhagic groups were compared.

Results: Fifteen of 37 (40.5 %) patients presented with hemorrhage were associated with smaller BAVM volume and the presence of intranidal aneurysm and exclusive deep venous drainage. The median interval between the diagnostic and stereotactic DSA was 49 days and did not differ between the groups. In both groups, the inter-exam QDSA measurements were more reliable for drainage veins and transnidal time (ICCs ranged from 0.38-0.93) than for feeding arteries (ICCs ranged from 0.01-0.74). Among the venous parameters, the hemorrhagic group had lower peak density, area under the curve, inflow gradient, and outflow gradient on both DSA exams and larger full width at half maximum and stasis index on the stereotactic DSA exam than the nonhemorrhagic group.

Conclusions: In BAVMs, the QDSA measurements for veins are more reliable than those for arteries. QDSA analysis reflecting stagnant venous drainage is associated with BAVM hemorrhage, but may be confounded by the acute hemodynamic change after hemorrhage.
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http://dx.doi.org/10.1016/j.ejrad.2020.109455DOI Listing
January 2021

Does the Diffuseness of the Nidus Affect the Outcome of Stereotactic Radiosurgery in Patients with Unruptured Cerebral Arteriovenous Malformations?

Stereotact Funct Neurosurg 2021 2;99(2):113-122. Epub 2020 Dec 2.

Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan,

Background: We proposed an algorithm to automate the components within the identification of components within the nidus of cerebral arteriovenous malformations (AVMs) which may be used to analyze the relationship between its diffuseness and treatment outcomes following stereotactic radiosurgery (SRS).

Objectives: to determine the impact of the diffuseness of the AVM nidus on SRS outcomes.

Methods: This study conducted regular follow-ups of 209 patients with unruptured AVMs who underwent SRS. The diffuseness of the AVM nidus was estimated by quantifying the proportions of vascular nidal component, brain parenchyma, and cerebrospinal fluid in T2-weighted MRIs. We used Cox regression analysis to characterize the association between nidal diffuseness and treatment outcomes in terms of obliteration rate and radiation-induced change (RICs) rate following SRS.

Results: The median AVM volume was 20.7 cm3. The median duration of imaging follow-up was 51 months after SRS. The overall AVM obliteration rate was 68.4%. RICs were identified in 156 of the 209 patients (74.6%). The median proportions of the nidus of AVM and brain parenchyma components within the prescription isodose range were 30.2 and 52.2%, respectively. Cox regression multivariate analysis revealed that the only factor associated with AVM obliteration rate after SRS was AVM volume. However, a larger AVM volume (>20 mL) and a larger proportion of brain parenchyma (>50%) within the prescription isodose range were both correlated with a higher RIC rate following SRS.

Conclusions: The diffuseness of the nidus indeed appears to affect the RIC rate following SRS in patients with unruptured AVMs.
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http://dx.doi.org/10.1159/000510683DOI Listing
December 2020

Prediction of pseudoprogression and long-term outcome of vestibular schwannoma after Gamma Knife radiosurgery based on preradiosurgical MR radiomics.

Radiother Oncol 2021 02 5;155:123-130. Epub 2020 Nov 5.

Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Background And Purpose: Gamma Knife radiosurgery (GKRS) is a safe and effective treatment modality with a long-term tumor control rate over 90% for vestibular schwannoma (VS). However, numerous tumors may undergo a transient pseudoprogression during 6-18 months after GKRS followed by a long-term volume reduction. The aim of this study is to determine whether the radiomics analysis based on preradiosurgical MRI data could predict the pseudoprogression and long-term outcome of VS after GKRS.

Materials And Methods: A longitudinal dataset of patients with VS treated by single GKRS were retrospectively collected. Overall 336 patients with no previous craniotomy for tumor removal and a median of 65-month follow-up period after radiosurgery were finally included in this study. In total 1763 radiomic features were extracted from the multiparameteric MRI data before GKRS followed by the machine-learning classification.

Results: We constructed a two-level machine-learning model to predict the long-term outcome and the occurrence of transient pseudoprogression after GKRS separately. The prediction of long-term outcome achieved an accuracy of 88.4% based on five radiomic features describing the variation of T2-weighted intensity and inhomogeneity of contrast enhancement in tumor. The prediction of transient pseudoprogression achieved an accuracy of 85.0% based on another five radiomic features associated with the inhomogeneous hypointensity pattern of contrast enhancement and the variation of T2-weighted intensity.

Conclusion: The proposed machine-learning model based on the preradiosurgical MR radiomics provides a potential to predict the pseudoprogression and long-term outcome of VS after GKRS, which can benefit the treatment strategy in clinical practice.
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http://dx.doi.org/10.1016/j.radonc.2020.10.041DOI Listing
February 2021

Noninvasive Characterization of Human Glymphatics and Meningeal Lymphatics in an in vivo Model of Blood-Brain Barrier Leakage.

Ann Neurol 2021 01 23;89(1):111-124. Epub 2020 Oct 23.

Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.

Objective: To evaluate human glymphatics and meningeal lymphatics noninvasively.

Methods: This prospective study implemented 3-dimensional (3D) isotropic contrast-enhanced T2 fluid-attenuated inversion recovery (CE-T2-FLAIR) imaging with a 3T magnetic resonance machine to study cerebral glymphatics and meningeal lymphatics in patients with reversible cerebral vasoconstriction syndrome (RCVS) with (n = 92) or without (n = 90) blood-brain barrier (BBB) disruption and a diseased control group with cluster headache (n = 35). The contrast agent gadobutrol (0.2mmol/kg [0.2ml/kg]) was administered intravenously in all study subjects.

Results: In total, 217 patients (182 RCVS, 35 cluster headache) were analyzed and separated into 2 groups based on the presence or absence of visible gadolinium (Gd) leakage. Para-arterial tracer enrichment was clearly depicted in those with overt BBB disruption, while paravenous and parasinus meningeal contrast enrichment was evident in both groups. Paravenous and parasinus contrast enrichment remained in RCVS patients in the remission stage and in cluster headache patients, suggesting that these meningeal lymphatic channels were universal anatomical structures rather than being phase- or condition-specific. Additionally, we demonstrated nodular leptomeningeal enhancement in 32.3% of participants, which might represent potential lymphatic reservoirs. Four selected RCVS patients who received consecutive contrasted 3D isotropic FLAIR imaging after gadobutrol administration showed that the Gd persisted for at least 54 minutes and was completely cleared within 18 hours.

Interpretation: This large-scale in vivo study successfully demonstrated the putative human para-arterial glymphatic transports and meningeal lymphatics by clear depiction of para-arterial, parasinus, and paravenous meningeal contrast enrichment using high-resolution 3D isotropic CE-T2-FLAIR imaging noninvasively; this technique may serve as a basis for further studies to delineate clinical relevance of glymphatic clearance. ANN NEUROL 2021;89:111-124.
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http://dx.doi.org/10.1002/ana.25928DOI Listing
January 2021

Combining analysis of multi-parametric MR images into a convolutional neural network: Precise target delineation for vestibular schwannoma treatment planning.

Artif Intell Med 2020 07 20;107:101911. Epub 2020 Jun 20.

National Yang-Ming University, Department of Biomedical Imaging and Radiological Sciences, Taipei, Taiwan; National Yang-Ming University, Institute of Biophotonics, Taipei, Taiwan; Brain Research Center, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Manual delineation of vestibular schwannoma (VS) by magnetic resonance (MR) imaging is required for diagnosis, radiosurgery dose planning, and follow-up tumor volume measurement. A rapid and objective automatic segmentation method is required, but problems have been encountered due to the low through-plane resolution of standard VS MR scan protocols and because some patients have non-homogeneous cystic areas within their tumors. In this study, we retrospectively collected multi-parametric MR images from 516 patients with VS; these were extracted from the Gamma Knife radiosurgery planning system and consisted of T1-weighted (T1W), T2-weighted (T2W), and T1W with contrast (T1W + C) images. We developed an end-to-end deep-learning-based method via an automatic preprocessing pipeline. A two-pathway U-Net model involving two sizes of convolution kernel (i.e., 3 × 3 × 1 and 1 × 1 × 3) was used to extract the in-plane and through-plane features of the anisotropic MR images. A single-pathway model that adopted the same architecture as the two-pathway model, but used a kernel size of 3 × 3 × 3, was also developed for comparison purposes. In addition, we used multi-parametric MR images with different image contrasts as the model training input in order to effectively segment tumors with solid as well as cystic parts. The results of the automatic segmentation demonstrated that (1) the two-pathway model outperformed single-pathway model in terms of dice scores (0.90 ± 0.05 versus 0.87 ± 0.07); both of them having been trained using the T1W, T1W + C and T2W anisotropic MR images, (2) the optimal single-parametric two-pathway model (dice score: 0.88 ± 0.06) was then trained using the T1W + C images, and (3) the two-pathway models trained using bi-parametric (T1W + C and T2W) and tri-parametric (T1W, T2W, and T1W + C) images outperformed the model trained using the single-parametric (T1W + C) images (dice scores: 0.89 ± 0.05 and 0.90 ± 0.05, respectively, larger than 0.88 ± 0.06) because it showed improved segmentation of the non-homogeneous parts of the tumors. The proposed two-pathway U-Net model outperformed the single-pathway U-Net model when segmenting VS using anisotropic MR images. The multi-parametric models effectively improved on the defective segmentation obtained using the single-parametric models by separating the non-homogeneous tumors into their solid and cystic parts.
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http://dx.doi.org/10.1016/j.artmed.2020.101911DOI Listing
July 2020

Repeated gamma knife radiosurgery enables longer tumor control in cases of highly-recurrent intracranial ependymoma.

J Neurooncol 2020 Jun 13;148(2):363-372. Epub 2020 May 13.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Purpose: Stereotactic radiosurgery (SRS) is a potential re-irradiation treatment for recurrent intracranial ependymoma after prior radiation therapy. The purpose of this study was to examine the efficacy and safety of repeated SRS in the treatment of recurrent intracranial ependymomas.

Methods: This is a retrospective study of consecutive patients with residual or recurrent intracranial ependymomas who were treated with SRS between 1993 and 2018. Tumor progression was defined as a ≥ 10% increase in tumor volume. Tumor regression was defined as a ≥ 10% reduction in tumor volume. A tumor that remained within 10% of its original volume was defined as stable. Tumor control comprised tumor regression and stability. Time-dependent analyses were performed using two treatment failure endpoint definitions: (1) evidence of local tumor progression or distant metastasis (single SRS analysis), and (2) lack of tumor response to SRS (repeated SRS analysis). These analyses were adjusted for the competing risk of death.

Results: The study comprised 37 patients (65 intracranial ependymomas) who underwent multiple SRS sessions (range: 1-7). Median age was 10.2 years (range: 0.8-53.8 years), and median tumor volume was 1.5 mL (range: 0.01-22.5 mL). The median radiation dose was 13.3 Gy (range: 7.9-22.0 Gy) at a median isodose line of 57% (range: 50-90%). Overall tumor control rates in the single SRS analysis adjusting for the competing risk of death were 53.6%, 30.5%, and 23.6% at 1, 3, and 5 years, respectively. Overall tumor control rates in the repeated SRS analysis adjusting for the competing risk of death were 70.6%, 50.4%, and 43.1% at 1, 3, and 5 years, respectively. Prior gross total resection was the only independent predictor of overall tumor control after SRS (aHR = 25.62 (1.55-422.1), p = 0.02).

Conclusions: Repeated GKRS appeared to be an effective treatment strategy for recurrent or residual intracranial ependymomas, with acceptable complication rates.
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http://dx.doi.org/10.1007/s11060-020-03531-7DOI Listing
June 2020

Supratentorial and Infratentorial Lesions in Spinocerebellar Ataxia Type 3.

Front Neurol 2020 3;11:124. Epub 2020 Mar 3.

Brain Research Center, National Yang-Ming University, Taipei, Taiwan.

Spinocerebellar ataxia type 3 (SCA) is a cerebellum-dominant degenerative disorder that is characterized primarily by infratentorial damage, although less severe supratentorial involvement may contribute to the clinical manifestation. These impairments may result from the efferent loss of the cerebellar cortex and degeneration of the cerebral cortex. We used the three-dimensional fractal dimension (3D-FD) method to quantify the morphological changes in the supratentorial regions and assessed atrophy in the relatively focal regions in patients with SCA3. A total of 48 patients with SCA3 and 50 sex- and age-matched healthy individuals, as the control group, participated in this study. The 3D-FD method was proposed to distinguish 97 automatic anatomical label regions of gray matter (left cerebrum: 45, right cerebrum: 45, cerebellum: 7) between healthy individuals and patients with SCA3. Patients with SCA3 exhibited reduced brain complexity within both the traditional olivopontocerebellar atrophy (OPCA) pattern and specific supratentorial regions. The study results confirmed the extensive involvement of extracerebellar regions in SCA3. The atrophied regions of SCA3 in infratentorial and supratentorial cortex showed a wide range of overlapped areas as in two functional cortexes, namely cerebellum-related cortex and basal ganglia-related cortex. Our results found that the atrophy of the SCA3 are not only limited in the infratentorial regions. Both cerebellar related cortex and basal ganglia related cortex were affected in the disease process of SCA3. Our findings might correlate to the common symptoms of SCA3, such as ataxia, Parkinsonism, dysarthria, and dysmetria. SCA3 should no longer be considered a disease limited to the cerebellum and its connections; rather, it should be considered a pathology affecting the whole brain.
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http://dx.doi.org/10.3389/fneur.2020.00124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062793PMC
March 2020

Magnetic resonance imaging as a single diagnostic tool for verifying radiosurgery outcomes of cavernous sinus dural arteriovenous fistula.

Eur J Radiol 2020 Apr 6;125:108866. Epub 2020 Feb 6.

School of Medicine, National Yang Ming University, Taipei, Taiwan; Neurological Institute, Department of Neurosurgery, Taipei Veterans General Hospital, Taipei, Taiwan.

Purpose: MRI and MR angiography (MRA) are noninvasive methods for examining cavernous sinus dural arteriovenous fistulas (CSDAVFs) after radiosurgery. In this study, we investigated the accuracy of unenhanced MRI/3-dimensional time-of-flight (3D TOF) MRA in evaluating CSDAVF obliteration as compared with digital subtraction angiography (DSA).

Methods: From 1995-2012, 48 cases of CSDAVFs received Gamma Knife surgery (GKS) and had undergone both unenhanced MRI/3D TOF MRA and DSA for posttreatment evaluation. Two blinded observers independently interpreted the results of MRI/MRA. The results of MRI/MRA were compared with those of DSA. The sensitivity (the probability of MRI/MRA showing obliteration when DSA showed complete obliteration), specificity, positive predictive value, and negative predictive value for CSDAVF obliteration were reported.

Results: The median interval between the final MRI/MRA and the subsequent DSA was 2 months. Follow-up DSA revealed that 38 of 48 (79.2 %) CSDAVFs were completely obliterated. The results of interobserver agreement assessment showed almost perfect agreement between the 2 observers. For unenhanced MRI/3D TOF MRA, the observed sensitivity was 84.2 %, specificity was 100 %, positive predictive value was 100 %, and negative predictive value was 62.5 %.

Conclusions: Unenhanced MRI/3D TOF MRA alone may be adequate to document the complete obliteration of CSDAVFs after GKS. Time-resolved MRA or DSA can be reserved for a suspected residual CSDAVF after a sufficient latency period after GKS.
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http://dx.doi.org/10.1016/j.ejrad.2020.108866DOI Listing
April 2020

Radiomics as prognostic factor in brain metastases treated with Gamma Knife radiosurgery.

J Neurooncol 2020 Feb 4;146(3):439-449. Epub 2020 Feb 4.

Professional Master Program in Artificial Intelligence in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Purpose: Gamma Knife radiosurgery (GKRS) is a non-invasive procedure for the treatment of brain metastases. This study sought to determine whether radiomic features of brain metastases derived from pre-GKRS magnetic resonance imaging (MRI) could be used in conjunction with clinical variables to predict the effectiveness of GKRS in achieving local tumor control.

Methods: We retrospectively analyzed 161 patients with non-small cell lung cancer (576 brain metastases) who underwent GKRS for brain metastases. The database included clinical data and pre-GKRS MRI. Brain metastases were demarcated by experienced neurosurgeons, and radiomic features of each brain metastasis were extracted. Consensus clustering was used for feature selection. Cox proportional hazards models and cause-specific proportional hazards models were used to correlate clinical variables and radiomic features with local control of brain metastases after GKRS.

Results: Multivariate Cox proportional hazards model revealed that higher zone percentage (hazard ratio, HR 0.712; P = .022) was independently associated with superior local tumor control. Similarly, multivariate cause-specific proportional hazards model revealed that higher zone percentage (HR 0.699; P = .014) was independently associated with superior local tumor control.

Conclusions: The zone percentage of brain metastases, a radiomic feature derived from pre-GKRS contrast-enhanced T1-weighted MRIs, was found to be an independent prognostic factor of local tumor control following GKRS in patients with non-small cell lung cancer and brain metastases. Radiomic features indicate the biological basis and characteristics of tumors and could potentially be used as surrogate biomarkers for predicting tumor prognosis following GKRS.
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http://dx.doi.org/10.1007/s11060-019-03343-4DOI Listing
February 2020

Gamma Knife radiosurgery for cerebral cavernous malformation.

Sci Rep 2019 12 24;9(1):19743. Epub 2019 Dec 24.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

This is a retrospective study examining the efficacy and safety of Gamma Knife radiosurgery (GKS) in treating patients with cerebral cavernous malformations (CCMs). Between 1993 and 2018, 261 patients with 331 symptomatic CCMs were treated by GKS. The median age was 39.9 years and females were predominant (54%). The median volume of CCMs was 3.1 mL. The median margin dose was 11.9 Gy treat to a median isodose level of 59%. Median clinical and imaging follow-up times were 69 and 61 months, respectively. After the initial hemorrhage that led to CCM diagnosis, 136 hemorrhages occurred in the period prior to GKS (annual incidence = 23.6%). After GKS, 15 symptomatic hemorrhages occurred within the first 2 years of follow-up (annual incidence = 3.22%), and 37 symptomatic hemorrhages occurred after the first 2 years of follow-up (annual incidence = 3.16%). Symptomatic radiation-induced complication was encountered in 8 patients (3.1%). Mortality related to GKS occurred in 1 patient (0.4%). In conclusion, GKS decreased the risk of hemorrhage in CCM patients presenting with symptomatic hemorrhage. GKS is a viable alternative treatment option for patients with surgically-inaccessible CCMs or significant medical comorbidities.
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http://dx.doi.org/10.1038/s41598-019-56119-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930272PMC
December 2019

Stagnant Venous Outflow Predicts Brain Arteriovenous Malformation Obliteration After Gamma Knife Radiosurgery Without Prior Intervention.

Neurosurgery 2020 08;87(2):338-347

Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Gamma Knife radiosurgery (GKRS) obliterates 65% to 82% of brain arteriovenous malformations (BAVMs).

Objective: To explore the impact of hemodynamics on GKRS outcomes.

Methods: We retrospectively (2011-2017) included 98 patients with BAVMs who had received GKRS alone. Two evaluators, blinded to the outcomes, analyzed the pre-GKRS angiography and magnetic resonance images to obtain the morphological characteristics and quantitative digital subtraction angiography (QDSA) parameters. The venous stasis index was defined as the inflow gradient divided by the absolute value of the outflow gradient. Patients' follow-up magnetic resonance or digital subtraction angiography images were evaluated for the presence of complete obliteration (CO). Cox regression and Kaplan-Meier analyses were conducted to determine the correlations between the parameters and outcomes.

Results: Among the 98 patients, 63 (63.4%) achieved CO after GKRS at a median latency period of 31 mo. In multivariable analyses with adjustments for age and sex, increased BAVM volume (hazard ratio (HR) 0.949, P = .022) was an independent characteristic predictor, and venous stenosis (HR 2.595, P = .009), venous rerouting (HR 0.375, P = .022), and larger stasis index (HR 1.227, P = .025) were independent angiographic predictors of CO. BAVMs with a stasis index of >1.71 had a higher 36-mo probability of CO than those with a stasis index of ≤1.71 (61.1% vs 26.7%, P < .001).

Conclusion: BAVMs with a larger stasis index, indicating more stagnant venous outflow, may predict obliteration after GKRS. QDSA analysis may help in predicting BAVM treatment outcomes and making therapeutic decisions.
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http://dx.doi.org/10.1093/neuros/nyz507DOI Listing
August 2020

Epidermal growth factor receptor mutations: association with favorable local tumor control following Gamma Knife radiosurgery in patients with non-small cell lung cancer and brain metastases.

J Neurosurg 2019 Jun 21:1-8. Epub 2019 Jun 21.

1Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital.

Objective: The presence of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) has been associated with elevated radiosensitivity in vitro. However, results from clinical studies on radiosensitivity in cases of NSCLC with EGFR mutations are inconclusive. This paper presents a retrospective analysis of patients with NSCLC who underwent regular follow-up imaging after radiotherapy for brain metastases (BMs). The authors also investigated the influence of EGFR mutations on the efficacy of Gamma Knife radiosurgery (GKRS).

Methods: This study included 264 patients (1069 BMs) who underwent GKRS treatment and for whom EGFR mutation status, demographics, performance status, and tumor characteristics were available. Radiological images were obtained at 3 months after GKRS and at 3-month intervals thereafter. Kaplan-Meier plots and Cox regression analysis were used to correlate EGFR mutation status and other clinical features with tumor control and overall survival.

Results: The tumor control rates and overall 12-month survival rates were 87.8% and 65.5%, respectively. Tumor control rates in the EGFR mutant group versus the EGFR wild-type group were 90.5% versus 79.4% at 12 months and 75.0% versus 24.5% at 24 months. During the 2-year follow-up period after SRS, the intracranial response rate in the EGFR mutant group was approximately 3-fold higher than that in the wild-type group (p < 0.001). Cox regression multivariate analysis identified EGFR mutation status, extracranial metastasis, primary tumor control, and prescribed margin dose as predictors of tumor control (p = 0.004, p < 0.001, p = 0.004, and p = 0.026, respectively). Treatment with a combination of GKRS and tyrosine kinase inhibitors (TKIs) was the most important predictor of overall survival (p < 0.001).

Conclusions: The current study demonstrated that, among patients with NSCLC-BMs, EGFR mutations were independent prognostic factors of tumor control. It was also determined that a combination of GKRS and TKI had the most pronounced effect on prolonging survival after SRS. In select patient groups, treatment with SRS in conjunction with EGFR-TKIs provided effective tumor control for NSCLC-BMs.
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http://dx.doi.org/10.3171/2019.4.JNS19446DOI Listing
June 2019

Treatment Outcomes of Cavernous Sinus Dural Arteriovenous Fistulas: Comparison of Radiosurgery and Endovascular Embolisation.

Clin Neuroradiol 2020 Jun 16;30(2):321-330. Epub 2019 May 16.

Neurologic Institute, Department of Neurosurgery, Taipei Veterans General Hospital, 201 Shipai Rd, Sec 2, Beitou District, 112, Taipei, Taiwan, ROC.

Background And Purpose: Endovascular treatment (EVT) and stereotaxic gamma-knife radiosurgery (GKRS) can both effectively treat cavernous sinus dural arteriovenous fistulas (CSDAVF). This study compared the prognostic factors and treatment effectiveness of GKRS and EVT for different CSDAVF types.

Methods: The charts of 200 patients undergoing GKRS and 105 patients undergoing EVT were reviewed for data on symptoms (e.g. orbital, cavernous, ocular, and cerebral). The CSDAVFs were classified into proliferative, restrictive, and late restrictive types. The prognostic factors for complete obliteration (CO) were evaluated in both the GKRS and EVT groups and the latent period to CO was measured. For statistical analysis χ-tests were used to compare final CO rates for EVT and GKRS across the three CSDAVF types.

Results: The EVT and cavernous symptoms were significant independent predictors of CO. The CO rate after EVT (97.9%) was significantly higher than that after GKRS (63.5%) for restrictive CSDAVFs (P < 0.001) but not for proliferative or late restrictive types. In the GKRS group, cavernous symptoms (hazard ratio, HR: 0.557) and target volume (HR: 0.853) predicted CO, but only target volume remained significant in multivariate analysis. In the EVT group, the latent period to CO was shortest for restrictive CSDAVFs (3.2 ± 1.6 months, P = 0.05).

Conclusion: Angioarchitecture did not affect treatment outcomes. Cavernous symptoms were strongly associated with lower complete obliteration rates in the GKRS but not the EVT group. The EVT method remains the treatment of choice, especially for restrictive CSDAVFs; however, compared to EVT, GKRS had lower complication rates and similar therapeutic effects for proliferative type fistulas.
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http://dx.doi.org/10.1007/s00062-019-00787-zDOI Listing
June 2020

Early recovery of interhemispheric functional connectivity after corpus callosotomy.

Epilepsia 2019 06 14;60(6):1126-1136. Epub 2019 May 14.

Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Objective: To investigate whether interhemispheric functional connectivity (FC) recovers in the first year after total callosotomy.

Methods: Eight epilepsy patients undergoing total callosotomy were recruited. Resting-state functional magnetic resonance imaging was acquired before and after surgery. The precallosotomy and postcallosotomy interhemispheric and intrahemispheric FC was analyzed by using graph theory and voxel-mirrored homotopic connectivity (VMHC). The seizure outcome was scored using the Engel surgical outcome scale.

Results: After callosotomy (mean postoperative interval = 4 months), the network density, average node degree, characteristic path length, and global efficiency of the whole interhemispheric networks were significantly decreased, compared to those in the precallosotomy networks. However, postcallosotomy interhemispheric FC and homotopic VMHC were not significantly reduced in bilateral frontal and temporal lobes. The network density and average node degree of the intrahemispheric networks were significantly increased. The characteristic path length and global efficiency of intrahemispheric networks were unchanged.

Significance: The interhemispheric FC may be preserved or recover early within the first postoperative year after total callosotomy, particularly in the frontal and anterior temporal lobes.
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http://dx.doi.org/10.1111/epi.14933DOI Listing
June 2019

Stasis index from hemodynamic analysis using quantitative DSA correlates with hemorrhage of supratentorial arteriovenous malformation: a cross-sectional study.

J Neurosurg 2019 Apr 26;132(5):1574-1582. Epub 2019 Apr 26.

1Department of Radiology and.

Objective: Assessments of hemorrhage risk based on angioarchitecture have yielded inconsistent results, and quantitative hemodynamic studies have been limited to small numbers of patients. The authors examined whether cerebral hemodynamic analysis using quantitative digital subtraction angiography (QDSA) can outperform conventional DSA angioarchitecture analysis in evaluating the risk of hemorrhage associated with supratentorial arteriovenous malformations (AVMs).

Methods: A cross-sectional study was performed by retrospectively reviewing adult supratentorial AVM patients who had undergone both DSA and MRI studies between 2011 and 2017. Angioarchitecture characteristics, DSA parameters, age, sex, and nidus volume were analyzed using univariate and multivariate logistic regression, and QDSA software analysis was performed on DSA images. Based on the QDSA analysis, a stasis index, defined as the inflow gradient divided by the absolute value of the outflow gradient, was determined. The receiver operating characteristic (ROC) curve was used to compare diagnostic performances of conventional DSA angioarchitecture analysis and analysis using hemodynamic parameters based on QDSA.

Results: A total of 119 supratentorial AVM patients were included. After adjustment for age at diagnosis, sex, and nidus volume, the exclusive deep venous drainage (p < 0.01), observed through conventional angioarchitecture examination using DSA, and the stasis index of the most dominant drainage vein (p = 0.02), measured with QDSA hemodynamic analysis, were independent risk factors for hemorrhage. The areas under the ROC curves for the conventional DSA method (0.75) and QDSA hemodynamics analysis (0.73) were similar. A venous stasis index greater than 2.18 discriminated the hemorrhage group with a sensitivity of 52.6% and a specificity of 81.5%.

Conclusions: In QDSA, a higher stasis index of the most dominant drainage vein is an objective warning sign associated with supratentorial AVM rupture. Risk assessments of AVMs using QDSA and conventional DSA angioarchitecture were equivalent. Because QDSA is a complementary noninvasive approach without extra radiation or contrast media, comprehensive hemorrhagic risk assessment of cerebral AVMs should include both DSA angioarchitecture and QDSA analyses.
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http://dx.doi.org/10.3171/2019.1.JNS183386DOI Listing
April 2019

Intra- and Inter-Modular Connectivity Alterations in the Brain Structural Network of Spinocerebellar Ataxia Type 3.

Entropy (Basel) 2019 Mar 23;21(3). Epub 2019 Mar 23.

Brain Research Center, National Yang-Ming University, Taipei 112, Taiwan.

In addition to cerebellar degeneration symptoms, patients with spinocerebellar ataxia type 3 (SCA3) exhibit extensive involvements with damage in the prefrontal cortex. A network model has been proposed for investigating the structural organization and functional mechanisms of clinical brain disorders. For neural degenerative diseases, a cortical feature-based structural connectivity network can locate cortical atrophied regions and indicate how their connectivity and functions may change. The brain network of SCA3 has been minimally explored. In this study, we investigated this network by enrolling 48 patients with SCA3 and 48 healthy subjects. A novel three-dimensional fractal dimension-based network was proposed to detect differences in network parameters between the groups. Copula correlations and modular analysis were then employed to categorize and construct the structural networks. Patients with SCA3 exhibited significant lateralized atrophy in the left supratentorial regions and significantly lower modularity values. Their cerebellar regions were dissociated from higher-level brain networks, and demonstrated decreased intra-modular connectivity in all lobes, but increased inter-modular connectivity in the frontal and parietal lobes. Our results suggest that the brain networks of patients with SCA3 may be reorganized in these regions, with the introduction of certain compensatory mechanisms in the cerebral cortex to minimize their cognitive impairment syndrome.
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http://dx.doi.org/10.3390/e21030317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7514800PMC
March 2019

Venous outflow restriction as a predictor of cavernous sinus dural arteriovenous fistula obliteration after Gamma Knife surgery.

J Neurosurg 2019 Jan 25:1-8. Epub 2019 Jan 25.

2Neurological Institute, Department of Neurosurgery, Taipei Veterans General Hospital; and.

Objective: Gamma Knife surgery (GKS) obliterates 65%-87% of cavernous sinus dural arteriovenous fistulas (CSDAVFs). However, the hemodynamic effect on GKS outcomes is relatively unknown. The authors thus used the classification scheme developed by Suh et al. to explore this effect.

Methods: The authors retrospectively (1993-2016) included 123 patients with CSDAVFs who received GKS alone at the institute and classified them as proliferative type (PT; n = 23), restrictive type (RT; n = 61), or late restrictive type (LRT; n = 39) after analyzing their pre-GKS angiography images. Treatment parameters, the presence of numerous arterial feeders, and venous drainage numbers were compared across the CSDAVF types. Patients' follow-up MR images were evaluated for the presence of complete obliteration. A Kaplan-Meier analysis was conducted to determine the correlation between CSDAVF types and outcomes.

Results: The 36-month probability of complete obliteration was 74.3% for all patients, with no significant differences across types (p = 0.56). PT had the largest radiation volume (6.5 cm3, p < 0.001), the most isocenters (5, p = 0.015) and venous drainage routes (3, p < 0.001), and the lowest peripheral dose (16.6 Gy, p = 0.011) and isodose level coverage (64.3%, p = 0.006). CSDAVFs presenting with ocular patterns were less likely to be completely obliterated (hazard ratio 0.531, p = 0.009). After adjustment for age, CSDAVFs with more venous drainage routes were less likely to be completely obliterated (hazard ratio 0.784, p = 0.039).

Conclusions: GKS is an equally effective treatment option for all 3 CSDAVF types. Furthermore, the number of venous drainage routes may help in predicting treatment outcomes and making therapeutic decisions.
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http://dx.doi.org/10.3171/2018.9.JNS182040DOI Listing
January 2019

Intervening Nidal Brain Parenchyma and Risk of Radiation-Induced Changes After Radiosurgery for Brain Arteriovenous Malformation: A Study Using an Unsupervised Machine Learning Algorithm.

World Neurosurg 2019 05 22;125:e132-e138. Epub 2019 Jan 22.

Biomedical Electronics Translational Research Center, National Chiao Tung University, Hsin-Chu, Taiwan; Institute of Electronics, National Chiao Tung University, Hsin-Chu, Taiwan. Electronic address:

Objective: To assess the sensitivity and specificity of arteriovenous malformation (AVM) nidal component identification and quantification using an unsupervised machine learning algorithm and to evaluate the association between intervening nidal brain parenchyma and radiation-induced changes (RICs) after stereotactic radiosurgery.

Methods: Fully automated segmentation via unsupervised classification with fuzzy c-means clustering was used to analyze the AVM nidus on T2-weighted magnetic resonance imaging studies. The proportions of vasculature, brain parenchyma, and cerebrospinal fluid were quantified. These were compared with the results from manual segmentation. The association between the brain parenchyma component and RIC development was assessed.

Results: The proposed algorithm was applied to 39 unruptured AVMs in 39 patients (17 female and 22 male patients), with a median age of 27 years. The median proportion of the constituents was as follows: vasculature, 31.3%; brain parenchyma, 48.4%; and cerebrospinal fluid, 16.8%. RICs were identified in 17 of the 39 patients (43.6%). Compared with manual segmentation, the automated algorithm was able to achieve a Dice similarity index of 79.5% (sensitivity, 73.5%; specificity, 85.5%). RICs were associated with a greater proportion of intervening nidal brain parenchyma (52.0% vs. 45.3%; P = 0.015). Obliteration was not associated with greater proportions of nidal vasculature (36.0% vs. 31.2%; P = 0.152).

Conclusions: The automated segmentation algorithm was able to achieve classification of the AVM nidus components with relative accuracy. Greater proportions of intervening nidal brain parenchyma were associated with RICs.
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http://dx.doi.org/10.1016/j.wneu.2018.12.220DOI Listing
May 2019

Empirical versus progression-guided stereotactic radiosurgery for non-functional pituitary macroadenomas after subtotal resection.

J Neurooncol 2019 Apr 12;142(2):291-297. Epub 2019 Jan 12.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.

Objective: There is a lack of consensus regarding whether if residual non-functional macroadenomas (NFM) should undergo empirical stereotactic radiosurgery (SRS) or be monitored until tumor progression before SRS treatment. The aim of this study is to compare the risks and benefits of empirical versus progression-guided SRS for NFM after subtotal resection.

Methods: This is a retrospective study of consecutive NFM patients who subtotal surgical resection followed by SRS between 1999 and 2014. Patients were dichotomized into two groups: empirical SRS (SRS without evidence of tumor progression) and progression-guided SRS (SRS after demonstration of tumor progression) groups. Tumor response was categorized into: (1) regression, ≥ 10% decrease in tumor volume; (2) stable, < 10% increase or decrease in tumor volume; and (3) progression, ≥ 10% increase in tumor volume. Tumor control comprised stable tumor response and tumor regression.

Results: Of the 112 patients who underwent SRS for NFM, 106 patients were treated for residual NFM after surgical resection, and included in the final analysis. The empirical SRS and progression-guided SRS groups comprised 46 and 60 patients, respectively. Overall tumor control rate was 88.7%. Higher rate of tumor control was achieved in the empirical SRS group compared to the progression-guided SRS group (95.65% vs. 83.33%, p = 0.047). Rates of new visual field deficit, cranial neuropathy and endocrinopathy were comparable between the two groups. Empirical SRS group had higher rates of progression-free survival compared to progression-guided SRS group (p = 0.015). Actuarial progression-free survival rates for the empirical SRS group were 93.2%, 93.2%, and 81.5% at 3, 5, and 10 years after SRS. Actuarial progression-free survival rates for the progression-guided SRS were 86.4%, 82.1%, and 68.4% at 3, 5, and 10 years after SRS.

Conclusion: Empirical SRS offers higher rates of tumor control and progression-free survival compared to progression-guided SRS in patients with residual NFM after surgical resection. Rates of new hypopituitarism and cranial neuropathies were comparable between the two groups.
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http://dx.doi.org/10.1007/s11060-019-03095-1DOI Listing
April 2019

Impaired Efficiency and Resilience of Structural Network in Spinocerebellar Ataxia Type 3.

Front Neurosci 2018 17;12:935. Epub 2018 Dec 17.

Institute of Biophotonics and Brain Research Center, National Yang-Ming University, Taipei, Taiwan.

Recent studies have shown that the patients with spinocerebellar ataxia type 3 (SCA3) may not only have disease involvement in the cerebellum and brainstem but also in the cerebral regions. However, the relations between the widespread degenerated brain regions remains incompletely explored. In the present study, we investigate the topological properties of the brain networks of SCA3 patients ( = 40) constructed based on the correlation of three-dimensional fractal dimension values. Random and targeted attacks were applied to measure the network resilience of normal and SCA3 groups. The SCA3 networks had significantly smaller clustering coefficients ( < 0.05) and global efficiency ( < 0.05) but larger characteristic path length ( < 0.05) than the normal controls networks, implying loss of small-world features. Furthermore, the SCA3 patients were associated with reduced nodal betweenness ( < 0.001) in the left supplementary motor area, bilateral paracentral lobules, and right thalamus, indicating that the motor control circuit might be compromised. The SCA3 networks were more vulnerable to targeted attacks than the normal controls networks because of the effects of pathological topological organization. The SCA3 revealed a more sparsity and disrupted structural network with decreased values in the largest component size, mean degree, mean density, clustering coefficient, and global efficiency and increased value in characteristic path length. The cortico-cerebral circuits in SCA3 were disrupted and segregated into occipital-parietal (visual-spatial cognition) and frontal-pre-frontal (motor control) clusters. The cerebellum of SCA3 were segregated from cerebellum-temporal-frontal circuits and clustered into a frontal-temporal cluster (cognitive control). Therefore, the disrupted structural network presented in this study might reflect the clinical characteristics of SCA3.
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http://dx.doi.org/10.3389/fnins.2018.00935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304428PMC
December 2018

Fully automated tissue segmentation of the prescription isodose region delineated through the Gamma knife plan for cerebral arteriovenous malformation (AVM) using fuzzy C-means (FCM) clustering.

Neuroimage Clin 2019 19;21:101608. Epub 2018 Nov 19.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Background: Gamma knife radiosurgery (GKRS) is a common treatment for cerebral arterio-venous malformations (AVMs), particularly in cases where the malformation is deep-seated, large, or in eloquent areas of the brain. Unfortunately, these procedures can result in radiation injury to brain parenchyma. The fact that every AVM is unique in its vascular morphology makes it nearly impossible to exclude brain parenchyma from isodose radiation exposure during the formulation of a GKRS plan. Calculating the percentages of the various forms of tissue exposed to specific doses of radiation is crucial to understanding the clinical responses and causes of brain parenchyma injury following GKRS for AVM.

Methods: In this study, we developed a fully automated algorithm using unsupervised classification via fuzzy c-means clustering for the analysis of T2 weighted images used in a Gamma knife plan. This algorithm is able to calculate the percentages of nidus, brain tissue, and cerebrospinal fluid (CSF) within the prescription isodose radiation exposure region.

Results: The proposed algorithm was used to assess the treatment plan of 25 patients with AVM who had undergone GKRS. The Dice similarity index (SI) was used to determine the degree of agreement between the results obtained using the algorithm and a visually guided manual method (the gold standard) performed by an experienced neurosurgeon. In the nidus, the SI was (74.86 ± 1.30%) (mean ± standard deviation), the sensitivity was (83.05 ± 11.91)%, and the specificity was (86.73 ± 10.31)%. In brain tissue, the SI was (79.50 ± 6.01)%, the sensitivity was (73.05 ± 9.77)%, and the specificity was (85.53 ± 7.13)%. In the CSF, the SI was (69.57 ± 15.26)%, the sensitivity was (89.86 ± 5.87)%, and the specificity was (92.36 ± 4.35)%.

Conclusions: The proposed clustering algorithm provides precise percentages of the various types of tissue within the prescription isodose region in the T2 weighted images used in the GKRS plan for AVM. Our results shed light on the causes of brain radiation injury after GKRS for AVM. In the future, this system could be used to improve outcomes and avoid complications associated with GKRS treatment.
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http://dx.doi.org/10.1016/j.nicl.2018.11.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413475PMC
December 2019

A single-institution study of predisposing factors of patients with BAVMs to flow-related aneurysm.

J Formos Med Assoc 2019 Mar 5;118(3):707-712. Epub 2018 Sep 5.

Department of Neurosurgery, Taipei Veterans General Hospital and National Yang-Ming University, School of Medicine, Taipei, Taiwan.

Background And Purpose: The goal of this study was to assess the potential risk factors leading to flow-related aneurysm (FA) formation in patients with brain arteriovenous malformations (BAVMs) in Taiwanese.

Methods: We recruited 890 patients with BAVMs: 72 had FA(s) and 818 did not. Several factors were assessed including patient's age, gender, BAVM volume and location, and Spetzler-Martin grade.

Results: The 890 patients with BAVM had a mean age of 30 years (range: 2-84), mean BAVM volume of 10.6 mL (range: 0.13-91.4). BAVMs were ruptured in 42% of patients. Compared to BAVM patients without FAs, the 72 patients with FAs had older age (mean 41 yrs vs 31 yrs, p < 0.001); larger average BAVM volume (39.6 mL vs 16.1 mL, p < 0.001). No statistical significance in Spetzler-Martin grades (χ value = 8.687 and p = 0.122) was found in terms of formation of FA. FA demonstrated similar gender distribution and BAVM location distribution (the χ-value was 0.242 and 0.812, respectively).

Conclusion: Patients with older age and large BAVM volume are more prone to FA. Gender, BAVM location, and BAVM grade are not statistically significant predisposing factors for FA.
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http://dx.doi.org/10.1016/j.jfma.2018.08.016DOI Listing
March 2019
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