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Yi-Chieh Hung, Cheng-Chia Lee, Kang-Du Liu, Wen-Yuh Chung, David Hung-Chi Pan and Huai-Che Yang

Object

The authors evaluated individual anatomical variations in the trigeminal nerves of patients with medically intractable trigeminal neuralgia and clarified the relationships among the variations, radiosurgical target locations, and the clinical outcomes after high-dose Gamma Knife surgery (GKS).

Methods

From 2006 through 2011, the authors conducted a retrospective review of 106 cases of primary or secondary trigeminal neuralgia consecutively treated with GKS targeting the dorsal root entry zone (DREZ) for which a maximal dose of 90 Gy and a 20% isodose line to the brainstem were used. A questionnaire was used to evaluate patients' pre- and post-GKS clinical conditions. To evaluate individual anatomical variations among trigeminal nerves, the authors used 3 parameters: the length of the trigeminal nerve in the cistern (nerve length), the length of the target between the radiation shot and the brainstem (targeting length), and the ratio between nerve length and targeting length (targeting ratio).

Results

The median length of the trigeminal nerves in the 106 patients was 9.6 mm (range 6.04−20.74 mm), the median targeting length was 3.8 mm (range 1.81−10.84 mm), and the median targeting ratio was 38% (range 13%− 80%). No statistically significant differences in pain relief and pain recurrence were detected among patients with these various nerve characteristics. However, radiation-induced facial hypesthesia correlated with nerve length and targeting ratio (p < 0.05) but not with absolute distance from the brainstem (targeting length).

Conclusions

In trigeminal neuralgia patients who received DREZ-targeted GKS, the rate of pain relief did not differ according to anatomical nerve variations. However, the frequency of facial hypesthesia was higher among patients in whom the nerve was longer (> 11 mm) or the targeting ratio was lower (< 36%). Adjusting the target according to the targeting ratio, especially for patients with longer nerves, can reduce facial hypesthesia and enable maintenance of effective pain control.

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Zhiyuan Xu, Carissa Carlson, John Snell, Matt Eames, Arik Hananel, M. Beatriz Lopes, Prashant Raghavan, Cheng-Chia Lee, Chun-Po Yen, David Schlesinger, Neal F. Kassell, Jean-Francois Aubry and Jason Sheehan

OBJECT

In biological tissues, it is known that the creation of gas bubbles (cavitation) during ultrasound exposure is more likely to occur at lower rather than higher frequencies. Upon collapsing, such bubbles can induce hemorrhage. Thus, acoustic inertial cavitation secondary to a 220-kHz MRI-guided focused ultrasound (MRgFUS) surgery is a serious safety issue, and animal studies are mandatory for laying the groundwork for the use of low-frequency systems in future clinical trials. The authors investigate here the in vivo potential thresholds of MRgFUS-induced inertial cavitation and MRgFUS-induced thermal coagulation using MRI, acoustic spectroscopy, and histology.

METHODS

Ten female piglets that had undergone a craniectomy were sonicated using a 220-kHz transcranial MRgFUS system over an acoustic energy range of 5600–14,000 J. For each piglet, a long-duration sonication (40-second duration) was performed on the right thalamus, and a short sonication (20-second duration) was performed on the left thalamus. An acoustic power range of 140–300 W was used for long-duration sonications and 300–700 W for short-duration sonications. Signals collected by 2 passive cavitation detectors were stored in memory during each sonication, and any subsequent cavitation activity was integrated within the bandwidth of the detectors. Real-time 2D MR thermometry was performed during the sonications. T1-weighted, T2-weighted, gradient-recalled echo, and diffusion-weighted imaging MRI was performed after treatment to assess the lesions. The piglets were killed immediately after the last series of posttreatment MR images were obtained. Their brains were harvested, and histological examinations were then performed to further evaluate the lesions.

RESULTS

Two types of lesions were induced: thermal ablation lesions, as evidenced by an acute ischemic infarction on MRI and histology, and hemorrhagic lesions, associated with inertial cavitation. Passive cavitation signals exhibited 3 main patterns identified as follows: no cavitation, stable cavitation, and inertial cavitation. Low-power and longer sonications induced only thermal lesions, with a peak temperature threshold for lesioning of 53°C. Hemorrhagic lesions occurred only with high-power and shorter sonications. The sizes of the hemorrhages measured on macroscopic histological examinations correlated with the intensity of the cavitation activity (R2 = 0.74). The acoustic cavitation activity detected by the passive cavitation detectors exhibited a threshold of 0.09 V·Hz for the occurrence of hemorrhages.

CONCLUSIONS

This work demonstrates that 220-kHz ultrasound is capable of inducing a thermal lesion in the brain of living swines without hemorrhage. Although the same acoustic energy can induce either a hemorrhage or a thermal lesion, it seems that low-power, long-duration sonication is less likely to cause hemorrhage and may be safer. Although further study is needed to decrease the likelihood of ischemic infarction associated with the 220-kHz ultrasound, the threshold established in this work may allow for the detection and prevention of deleterious cavitations.

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Cheng-Chia Lee, David Hung-Chi Pan, Wen-Yuh Chung, Kang-Du Liu, Huai-Che Yang, Hsiu-Mei Wu, Wan-Yuo Guo and Yang-Hsin Shih

Object

The authors retrospectively reviewed the efficacy and safety of Gamma Knife surgery (GKS) in patients with brainstem cavernous malformations (CMs). The CMs had bled repeatedly and placed the patients at high risk with respect to surgical intervention.

Methods

Between 1993 and 2010, 49 patients with symptomatic CMs were treated by GKS. The mean age in these patients was 37.8 years, and the predominant sex was female (59.2%). All 49 patients experienced at least 2 instances of repeated bleeding before GKS; these hemorrhages caused neurological deficits including cranial nerve deficits, hemiparesis, hemisensory deficits, spasticity, chorea or athetosis, and consciousness disturbance.

Results

The mean size of the CMs at the time of GKS was 3.2 cm3 (range 0.1–14.6 cm3). The mean radiation dose directed to the lesion was 11 Gy with an isodose level at 60.0%. The mean clinical and imaging follow-up time was 40.6 months (range 1.0–150.7 months). Forty-five patients participated in regularly scheduled follow-up. Twenty-nine patients (59.2%) were followed up for > 2 years, and 16 (32.7%) were followed up for < 2 years. The pre-GKS annual hemorrhage rate was 31.3% (69 symptomatic hemorrhages during a total of 220.3 patient-years). After GKS, 3 episodes of symptomatic hemorrhage were observed within the first 2 years of follow-up (4.29% annual hemorrhage rate), and 3 episodes of symptomatic hemorrhage were observed after the first 2 years of follow-up (3.64% annual hemorrhage rate). In this study of 49 patients, symptomatic radiation-induced complications developed in only 2 patients (4.1%; cyst formation in 1 patient and perifocal edema with neurological deficits in the other patient). There were no deaths in this group.

Conclusions

Gamma Knife surgery is effective in reducing the rate of recurrent hemorrhage. In the authors' experience, it was possible to control bleeding using a low-dose treatment. In addition, there were few symptomatic radiation-induced complications. As a result, the authors believe that GKS is a good alternative treatment for brainstem CMs.

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Cheng-Chia Lee, Michael A. Reardon, Benjamin Z. Ball, Ching-Jen Chen, Chun-Po Yen, Zhiyuan Xu, Max Wintermark and Jason Sheehan

OBJECT

The current gold standard for diagnosing arteriovenous malformation (AVM) and assessing its obliteration after stereotactic radiosurgery (SRS) is digital subtraction angiography (DSA). Recently, MRI and MR angiography (MRA) have become increasingly popular imaging modalities for the follow-up of patients with an AVM because of their convenient setup and noninvasiveness. In this study, the authors assessed the sensitivity and specificity of MRI/MRA in evaluating AVM nidus obliteration as assessed by DSA.

METHODS

The authors study a consecutive series of 136 patients who underwent SRS between January 2000 and December 2012 and who underwent regular clinical examinations, several MRI studies, and at least 1 post-SRS DSA follow- up evaluation at the University of Virginia. The average follow-up time was 47.3 months (range 10.1–165.2 months). Two blinded observers were enrolled to interpret the results of MRI/MRA compared with those of DSA. The sensitivity, specificity, positive predictive value, and negative predictive value for the obliteration of AVM were reported.

RESULTS

On the basis of DSA, 73 patients (53.7%) achieved final angiographic obliteration in a median of 28.8 months. The sensitivity (the probability of finding obliteration on MRI/MRA among those for whom complete obliteration was shown on DSA) was 84.9% for one observer (Observer 1) and 76.7% for the other (Observer 2). The specificity was 88.9% and 95.2%, respectively. The false-negative interpretations were significantly related to the presence of draining veins, perinidal edema on T2-weighted images, and the interval between the MRI/MRA and DSA studies.

CONCLUSIONS

MRI/MRA predicted AVM obliteration after SRS in most patients and can be used in their follow-up. However, because the specificity of MRI/MRA is not perfect, DSA should still be performed to confirm AVM nidus obliteration after SRS.

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Zhiyuan Xu, Cheng-Chia Lee, Arjun Ramesh, Adam C. Mueller, David Schlesinger, Or Cohen-Inbar, Han-Hsun Shih and Jason P. Sheehan

OBJECTIVE

Recent advancements in molecular biology have identified the BRAF mutation as a common mutation in melanoma. The wide use of BRAF kinase inhibitor (BRAFi) in patients with metastatic melanoma has been established. The objective of this study was to examine the impact of BRAF mutation status and use of BRAFi in conjunction with stereotactic radiosurgery (SRS).

METHODS

This was a single-center retrospective study. Patient's charts and electronic records were reviewed for date of diagnosis of primary malignancy, BRAF mutation status, chemotherapies used, date of the diagnosis of CNS metastases, date of SRS, survival, local tumor control after SRS, and adverse events. Patients were divided into 3 groups: Group A, those with mutant BRAF without BRAFi treatment (13 patients); Group B, those with mutant BRAF with BRAFi treatment (17 patients); and Group C, those with wild-type BRAF (35 patients). Within a cohort of 65 patients with the known BRAF mutation status and treated with SRS between 2010 and 2014, 436 individual brain metastases (BMs) were identified. Kaplan-Meier methodology was then used to compare survival based on each binary parameter.

RESULTS

Median survival times after the diagnosis of melanoma BM and after SRS were favorable in patients with a BRAF mutation and treated with SRS in conjunction with BRAFi (Group B) compared with the patients with wild-type BRAF (Group C, 23 vs 8 months and 13 vs 5 months, respectively; p < 0.01, log-rank test). SRS provided a local tumor control rate of 89.4% in the entire cohort of patients. Furthermore, the local control rate was improved in the patients treated with SRS in conjunction with BRAFi (Group B) compared with patients with wild-type (Group C) or with BRAF mutation but no BRAFi (Group A) as an adjunct treatment for BMs.

CONCLUSIONS

BRAF mutation status appears to play an important role as a potent prognostic factor in patients harboring melanoma BM. BRAFi in conjunction with SRS may benefit this group of patients in terms of BM survival and SRS with an acceptable safety profile.

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Cheng-Chia Lee, Jason P. Sheehan, Hideyuki Kano, Berkcan Akpinar, Roberto Martinez-Alvarez, Nuria Martinez-Moreno, Wan-Yuo Guo, L. Dade Lunsford and Kang-Du Liu

OBJECTIVE

Cavernous sinus hemangiomas (CSHs) are rare vascular tumors. A direct microsurgical approach usually results in massive hemorrhage and incomplete tumor resection. Although stereotactic radiosurgery (SRS) has emerged as a therapeutic alternative to microsurgery, outcome studies are few. Authors of the present study evaluated the role of SRS for CSH.

METHODS

An international multicenter study was conducted to review outcome data in 31 patients with CSH. Eleven patients had initial microsurgery before SRS, and the other 20 patients (64.5%) underwent Gamma Knife SRS as the primary management for their CSH. Median age at the time of radiosurgery was 47 years, and 77.4% of patients had cranial nerve dysfunction before SRS. Patients received a median tumor margin dose of 12.6 Gy (range 12–19 Gy) at a median isodose of 55%.

RESULTS

Tumor regression was confirmed by imaging in all 31 patients, and all patients had greater than 50% reduction in tumor volume at 6 months post-SRS. No patient had delayed tumor growth, new cranial neuropathy, visual function deterioration, adverse radiation effects, or hypopituitarism after SRS. Twenty-four patients had presented with cranial nerve disorders before SRS, and 6 (25%) of them had gradual improvement. Four (66.7%) of the 6 patients with orbital symptoms had symptomatic relief at the last follow-up.

CONCLUSIONS

Stereotactic radiosurgery was effective in reducing the volume of CSH and attaining long-term tumor control in all patients at a median of 40 months. The authors' experience suggests that SRS is a reasonable primary and adjuvant treatment modality for patients in whom a CSH is diagnosed.

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Zengpanpan Ye, Xiaolin Ai and Chao You

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Zengpanpan Ye, Xiaolin Ai and Chao You

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Chih-Chun Wu, Wan-Yuo Guo, Wen-Yuh Chung, Hisu-Mei Wu, Chung-Jung Lin, Cheng-Chia Lee, Kang-Du Liu and Huai-che Yang

OBJECTIVE

Gamma Knife surgery (GKS) is a promising treatment modality for patients with vestibular schwannomas (VSs), but a small percentage of patients have persistent postradiosurgical tumor growth. The aim of this study was to determine the clinical and quantitative MRI features of VS as predictors of long-term tumor control after GKS.

METHODS

The authors performed a retrospective study of all patients with VS treated with GKS using the Leksell Gamma Knife Unit between 2005 and 2013 at their institution. A total of 187 patients who had a minimum of 24 months of clinical and radiological assessment after radiosurgery were included in this study. Those who underwent a craniotomy with tumor removal before and after GKS were excluded. Study patients comprised 85 (45.5%) males and 102 (54.5%) females, with a median age of 52.2 years (range 20.4–82.3 years). Tumor volumes, enhancing patterns, and apparent diffusion coefficient (ADC) values were measured by region of interest (ROI) analysis of the whole tumor by serial MRI before and after GKS.

RESULTS

The median follow-up period was 60.8 months (range 24–128.9 months), and the median treated tumor volume was 3.54 cm3 (0.1–16.2 cm3). At last follow-up, imaging studies indicated that 150 tumors (80.2%) showed decreased tumor volume, 20 (10.7%) had stabilized, and 17 (9.1%) continued to grow following radiosurgery. The postradiosurgical outcome was not significantly correlated with pretreatment volumes or postradiosurgical enhancing patterns. Tumors that showed regression within the initial 12 months following radiosurgery were more likely to have a larger volume reduction ratio at last follow-up than those that did not (volume reduction ratio 55% vs 23.6%, respectively; p < 0.001). Compared with solid VSs, cystic VSs were more likely to regress or stabilize in the initial postradiosurgical 6–12-month period and during extended follow-up. Cystic VSs exhibited a greater volume reduction ratio at last follow-up (cystic vs solid: 67.6% ± 24.1% vs 31.8% ± 51.9%; p < 0.001). The mean preradiosurgical maximum ADC (ADCmax) values of all VSs were significantly higher for those with tumor regression or stabilization at last follow-up compared with those with progression (2.391 vs 1.826 × 10−3 mm2/sec; p = 0.010).

CONCLUSIONS

Loss of central enhancement after radiosurgery was a common phenomenon, but it did not correlate with tumor volume outcome. Preradiosurgical MRI features including cystic components and ADCmax values can be helpful as predictors of treatment outcome.