Diffusion tensor imaging in pediatric patients with dystonia.

BACKGROUND: Childhood-onset dystonia is often progressive and severely impairs a child´s life. The pathophysiology is very heterogeneous and treatment responses vary in patients with dystonia. Factors influencing treatment effects remain to be elucidated. We hypothesize that differences in brain connectivity and fiber coherence contribute to the heterogeneity in treatment response among pediatric patients with inherited and acquired dystonia. METHODS: Twenty patients with childhood-onset dystonia were retrospectively recruited including twelve patients with inherited or idiopathic, and eight patients with acquired dystonia (mean age 10 years; 8 female/12 male). Fiber density between the internal part of the globus pallidus and selective target regions, as well as the diffusion measures of fractional anisotropy (FA) and mean diffusivity (MD) were analyzed and compared between different etiologies. RESULTS: Patients with acquired dystonia presented higher fiber density to the premotor cortex and putamen and lower FA values in the thalamus compared to patients with inherited/idiopathic dystonia. MD in the premotor cortex was higher in patients with acquired dystonia, while it was lower in the thalamus. CONCLUSION: Diffusion MRI reveals microstructural and network alterations in patients with dystonia of different etiologies.

Use of dose-area product to assess plan quality in robotic radiosurgery.

PURPOSE: In robotic stereotactic radiosurgery (SRS), optimal selection of collimators from a set of fixed cones must be determined manually by trial and error. A unique and uniformly scaled metric to characterize plan quality could help identify Pareto-efficient treatment plans. METHODS: The concept of dose-area product (DAP) was used to define a measure (DAPratio) of the targeting efficiency of a set of beams by relating the integral DAP of the beams to the mean dose achieved in the target volume. In a retrospective study of five clinical cases of brain metastases with representative target volumes (range: 0.5-5.68 ml) and 121 treatment plans with all possible collimator choices, the DAPratio was determined along with other plan metrics (conformity index CI, gradient index R50%, treatment time, total number of monitor units TotalMU, radiotoxicity index f12, and energy efficiency index η50%), and the respective Spearman's rank correlation coefficients were calculated. The ability of DAPratio to determine Pareto efficiency for collimator selection at DAPratio < 1 and DAPratio < 0.9 was tested using scatter plots. RESULTS: The DAPratio for all plans was on average 0.95 ±â€¯0.13 (range: 0.61-1.31). Only the variance of the DAPratio was strongly dependent on the number of collimators. For each target, there was a strong or very strong correlation of DAPratio with all other metrics of plan quality. Only for R50% and η50% was there a moderate correlation with DAPratio for the plans of all targets combined, as R50% and η50% strongly depended on target size. Optimal treatment plans with CI, R50%, f12, and η50% close to 1 were clearly associated with DAPratio < 1, and plans with DAPratio < 0.9 were even superior, but at the cost of longer treatment times and higher total monitor units. CONCLUSIONS: The newly defined DAPratio has been demonstrated to be a metric that characterizes the target efficiency of a set of beams in robotic SRS in one single and uniformly scaled number. A DAPratio < 1 indicates Pareto efficiency. The trade-off between plan quality on the one hand and short treatment time or low total monitor units on the other hand is also represented by DAPratio.

Radiomics outperforms semantic features for prediction of response to stereotactic radiosurgery in brain metastases.

BACKGROUND: Brain metastases show different patterns of contrast enhancement, potentially reflecting hypoxic and necrotic tumor regions with reduced radiosensitivity. An objective evaluation of these patterns might allow a prediction of response to radiotherapy. We therefore investigated the potential of MRI radiomics in comparison with the visual assessment of semantic features to predict early response to stereotactic radiosurgery in patients with brain metastases. PATIENTS AND METHODS: In this retrospective study, 150 patients with 308 brain metastases from solid tumors (NSCLC in 53% of patients) treated by stereotactic radiosurgery (single dose of 17-20 Gy) were evaluated. The response of each metastasis (partial or complete remission vs. stabilization or progression) was assessed within 180 days after radiosurgery. Patterns of contrast enhancement in the pre-treatment T1-weighted MR images were either visually classified (homogenous, heterogeneous, necrotic ring-like) or subjected to a radiomics analysis. Random forest models were optimized by cross-validation and evaluated in a hold-out test data set (30% of metastases). RESULTS: In total, 221/308 metastases (72%) responded to radiosurgery. The optimal radiomics model comprised 10 features and outperformed the model solely based on semantic features in the test data set (AUC, 0.71 vs. 0.56; accuracy, 69% vs. 54%). The diagnostic performance could be further improved by combining semantic and radiomics features resulting in an AUC of 0.74 and an accuracy of 75% in the test data set. CONCLUSION: The developed radiomics model allowed prediction of early response to radiosurgery in patients with brain metastases and outperformed the visual assessment of patterns of contrast enhancement.

Impact of prescription isodose level and collimator selection on dose homogeneity and plan quality in robotic radiosurgery.

PURPOSE: In stereotactic radiosurgery (SRS), prescription isodoses and resulting dose homogeneities vary widely across different platforms and clinical entities. Our goal was to investigate the physical limitations of generating dose distributions with an intended level of homogeneity in robotic SRS. METHODS: Treatment plans for non-isocentric irradiation of 4 spherical phantom targets (volume 0.27-7.70 ml) and 4 clinical targets (volume 0.50-5.70 ml) were calculated using Sequential (phantom) or VOLOTM (clinical) optimizers (Accuray, Sunnyvale, CA, USA). Dose conformity, volume of 12 Gy isodose (V12Gy) as a measure for dose gradient, and treatment time were recorded for different prescribed isodose levels (PILs) and collimator settings. In addition, isocentric irradiation of phantom targets was examined, with dose homogeneity modified by using different collimator sizes. RESULTS: Dose conformity was generally high (nCI ≤ 1.25) and varied little with PIL. For all targets and collimator sets, V12Gy was highest for PIL ≥ 80% and lowest for PIL ≤ 65%. The impact of PIL on V12Gy was highest for isocentric irradiation and lowest for clinical targets (VOLOTM optimization). The variability of V12Gy as a function of collimator selection was significantly higher than that of PIL. V12Gy and treatment time were negatively correlated. Plans utilizing a single collimator with a diameter in the range of 70-80% of the target diameter were fastest, but showed the strongest dependence on PIL. CONCLUSION: Inhomogeneous dose distributions with PIL ≤ 70% can be used to minimize dose to normal tissue. PIL ≥ 90% is associated with a marked and significant increase in off-target dose exposure. Careful selection of collimators during planning is even more important.

Radiomics for prediction of radiation-induced lung injury and oncologic outcome after robotic stereotactic body radiotherapy of lung cancer: results from two independent institutions.

OBJECTIVES: To generate and validate state-of-the-art radiomics models for prediction of radiation-induced lung injury and oncologic outcome in non-small cell lung cancer (NSCLC) patients treated with robotic stereotactic body radiation therapy (SBRT). METHODS: Radiomics models were generated from the planning CT images of 110 patients with primary, inoperable stage I/IIa NSCLC who were treated with robotic SBRT using a risk-adapted fractionation scheme at the University Hospital Cologne (training cohort). In total, 199 uncorrelated radiomic features fulfilling the standards of the Image Biomarker Standardization Initiative (IBSI) were extracted from the outlined gross tumor volume (GTV). Regularized models (Coxnet and Gradient Boost) for the development of local lung fibrosis (LF), local tumor control (LC), disease-free survival (DFS) and overall survival (OS) were built from either clinical/ dosimetric variables, radiomics features or a combination thereof and validated in a comparable cohort of 71 patients treated by robotic SBRT at the Radiosurgery Center in Northern Germany (test cohort). RESULTS: Oncologic outcome did not differ significantly between the two cohorts (OS at 36 months 56% vs. 43%, p = 0.065; median DFS 25 months vs. 23 months, p = 0.43; LC at 36 months 90% vs. 93%, p = 0.197). Local lung fibrosis developed in 33% vs. 35% of the patients (p = 0.75), all events were observed within 36 months. In the training cohort, radiomics models were able to predict OS, DFS and LC (concordance index 0.77-0.99, p < 0.005), but failed to generalize to the test cohort. In opposite, models for the development of lung fibrosis could be generated from both clinical/dosimetric factors and radiomic features or combinations thereof, which were both predictive in the training set (concordance index 0.71- 0.79, p < 0.005) and in the test set (concordance index 0.59-0.66, p < 0.05). The best performing model included 4 clinical/dosimetric variables (GTV-Dmean, PTV-D95%, Lung-D1ml, age) and 7 radiomic features (concordance index 0.66, p < 0.03). CONCLUSION: Despite the obvious difficulties in generalizing predictive models for oncologic outcome and toxicity, this analysis shows that carefully designed radiomics models for prediction of local lung fibrosis after SBRT of early stage lung cancer perform well across different institutions.

Connectivity Patterns of Deep Brain Stimulation Targets in Patients with Gilles de la Tourette Syndrome.

Since 1999, several targets for deep brain stimulation (DBS) in Gilles de la Tourette syndrome (GTS) have emerged showing similar success rates. Studies using different tractography techniques have identified connectivity profiles associated with a better outcome for individual targets. However, GTS patients might need individualized therapy. The objective of this study is to analyze the connectivity profile of different DBS targets for GTS. We identified standard target coordinates for the centromedian nucleus/nucleus ventro-oralis internus (CM/Voi), the CM/parafascicular (CM-Pf) complex, the anteromedial globus pallidus internus (amGPi), the posteroventral GPi (pvGPi), the ventral anterior/ventrolateral thalamus (VA/VL), and the nucleus accumbens/anterior limb of the internal capsule (Nacc/ALIC). Probabilistic tractography was performed from the targets to different limbic and motor areas based on patient-specific imaging and a normative connectome (HCP). Our analysis showed significant differences between the connectivity profiles of standard DBS targets (p < 0.05). Among all targets, the pvGPi showed the strongest connection to the sensorimotor cortex, while the amGPi showed the strongest connection to the prefrontal cortex in patient-specific imaging. Differences were observed between the connectivity profiles when using probabilistic tractography based on patient data and HCP. Our findings showed that the connectivity profiles of different DBS targets to major motor and limbic areas differ significantly. In the future, these differences may be considered when planning DBS for GTS patients employing an individualized approach. There were compelling differences in connectivity profiles when using different tractography techniques.

Stereotactic radiosurgery of benign brain tumors in elderly patients: evaluation of outcome and toxicity.

BACKGROUND: Stereotactic radiosurgery (SRS) is widely accepted as a therapeutic option for meningiomas (M) and vestibular schwannomas (VS). However, data on outcome and toxicity in the elderly population have rarely been reported in detail. METHODS: All patients aged ≥ 65 years with M or VS who underwent single fraction SRS were included. Patient data were analyzed in terms of clinical tumor control and incidence of early and late treatment related complications, which were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), RESULTS: We identified 245 patients with benign brain tumors (129 M and 116 VS, median tumor volume 2.9 ml, range 0.1-28). The median age was 71 years (range 65-86) and the mean follow-up times were 42 months (range 2-181). Tumors were irradiated with a median dose of 12.4 Gy. Actuarial clinical and radiological tumor control rates at 2, 5, and 10 years after SRS were 98%, 93%, and 88%, respectively. Recurrent tumors after previous treatment had a higher probability of post-radiosurgical progression (p < 0.001). Permanent toxicity (CTCAE I/II) were noted in 5.7%. No severe adverse events were observed during early and late follow up, although patients > 70 years had a slightly higher risk for toxicity (p = 0.027). The presence and extent of co-morbidities had no significant influence on local tumor control or toxicity. CONCLUSION: SRS provides favorable tumor control with low risk for treatment-related severe complications. Thus, SRS should always be considered as treatment option for benign intracranial tumors (meningiomas, schwannomas), especially in the group of elderly patients.

Radiomics in radiation oncology-basics, methods, and limitations.

Over the past years, the quantity and complexity of imaging data available for the clinical management of patients with solid tumors has increased substantially. Without the support of methods from the field of artificial intelligence (AI) and machine learning, a complete evaluation of the available image information is hardly feasible in clinical routine. Especially in radiotherapy planning, manual detection and segmentation of lesions is laborious, time consuming, and shows significant variability among observers. Here, AI already offers techniques to support radiation oncologists, whereby ultimately, the productivity and the quality are increased, potentially leading to an improved patient outcome. Besides detection and segmentation of lesions, AI allows the extraction of a vast number of quantitative imaging features from structural or functional imaging data that are typically not accessible by means of human perception. These features can be used alone or in combination with other clinical parameters to generate mathematical models that allow, for example, prediction of the response to radiotherapy. Within the large field of AI, radiomics is the subdiscipline that deals with the extraction of quantitative image features as well as the generation of predictive or prognostic mathematical models. This review gives an overview of the basics, methods, and limitations of radiomics, with a focus on patients with brain tumors treated by radiation therapy.

Outcome and toxicity analysis of single dose stereotactic radiosurgery in vestibular schwannoma based on the Koos grading system.

Stereotactic radiosurgery (SRS) has evolved as widely accepted treatment option for small-sized (Koos I up to II) vestibular schwannoma (VS). For larger tumors (prevalent Koos VI), microsurgery or combined treatment strategies are mostly recommended. However, in patients not suited for microsurgery, SRS might also be an alternative to balance tumor control, hearing preservation and adverse effects. The purpose of this analysis was to evaluate the efficacy and toxicity of SRS for VS with regard to different Koos grades. All patients with untreated VS who received SRS at our center were included. Outcome analysis included tumor control, preservation of serviceable hearing based on median pure tone averages (PTA), and procedure-related adverse events rated by the Common Terminology Criteria for Adverse Events (CTCAE; v4.03) classification. In total, 258 patients (median age 58 years, range 21-84) were identified with a mean follow-up of 52 months (range 3-228 months). Mean tumor volume was 1.8 ml (range 0.1-18.5). The mean marginal dose was 12.3 Gy ± 0.6 (range 11-13.5). The cohort was divided into two groups: A (Koos grades I and II, n = 186) and B (Koos grades III and IV, n = 72). The actuarial tumor control rate was 98% after 2 years and 90% after 5 and 10 years. Koos grading did not show a significant impact on tumor control (p = 0.632) or hearing preservation (p = 0.231). After SRS, 18 patients (7%) had new transient or permanent symptoms classified by the CTCAE. The actuarial rate of CTCAE-free survival was not related to Koos grading (p = 0.093). Based on this selected population of Koos grade III and IV VS without or with only mild symptoms from brainstem compression, SRS can be recommended as the primary therapy with the advantage of low morbidity and satisfactory tumor control. The overall hearing preservation rate and toxicity of SRS was influenced by age and cannot be predicted by tumor volume or Koos grading alone.

Deep convolutional neural networks for automated segmentation of brain metastases trained on clinical data.

INTRODUCTION: Deep learning-based algorithms have demonstrated enormous performance in segmentation of medical images. We collected a dataset of multiparametric MRI and contour data acquired for use in radiosurgery, to evaluate the performance of deep convolutional neural networks (DCNN) in automatic segmentation of brain metastases (BM). METHODS: A conventional U-Net (cU-Net), a modified U-Net (moU-Net) and a U-Net trained only on BM smaller than 0.4 ml (sU-Net) were implemented. Performance was assessed on a separate test set employing sensitivity, specificity, average false positive rate (AFPR), the dice similarity coefficient (DSC), Bland-Altman analysis and the concordance correlation coefficient (CCC). RESULTS: A dataset of 509 patients (1223 BM) was split into a training set (469 pts) and a test set (40 pts). A combination of all trained networks was the most sensitive (0.82) while maintaining a specificity 0.83. The same model achieved a sensitivity of 0.97 and a specificity of 0.94 when considering only lesions larger than 0.06 ml (75% of all lesions). Type of primary cancer had no significant influence on the mean DSC per lesion (p = 0.60). Agreement between manually and automatically assessed tumor volumes as quantified by a CCC of 0.87 (95% CI, 0.77-0.93), was excellent. CONCLUSION: Using a dataset which properly captured the variation in imaging appearance observed in clinical practice, we were able to conclude that DCNNs reach clinically relevant performance for most lesions. Clinical applicability is currently limited by the size of the target lesion. Further studies should address if small targets are accurately represented in the test data.

Stereotactic Radiosurgery of Cavernous Sinus Meningiomas.

Objective Microsurgical resection of cavernous sinus meningiomas (CSM) is associated with a high rate of incomplete resection, recurrence, and the risk for permanent, severe cranial nerve deficits. Stereotactic radiosurgery (SRS) has evolved as alternative treatment for primary and recurrent CSM. Here, we report about the long-term clinical and radiological follow-up (FU) of a unique cohort of patients with CSM treated with LINAC or Cyberknife based SRS. Methods In this single-center retrospective analysis, we include all patients with CSM who underwent single fraction SRS between 1993 and 2016. Clinical and radiological tumor control were evaluated by the Kaplan-Meier method. Additionally, patient data were analyzed in terms of symptom control and incidence of side effects rated by the common terminology criteria for adverse events (CTCAE; v4.03). Results 116 patients (female/male = 91/25; median age, 54 years; range, 33-82 years) were included. Mean tumor volume was 5.7 ± 3.3 cm 3 (range, 0.6-16.2 cm 3 ), the median marginal dose was 12.6 Gy applied to isodose levels of 75%. Median clinical FU was 55 months (range, 3-226 months). Tumor control was 98% after 2 and 5 years and 90% after 10 years. Twelve patients (10.3%) had permanent or transient radiation related toxicity (CTCAE I-III). An improvement of symptoms was observed in 26.7% of the symptomatic patients ( n = 20 of 75). Conclusion SRS for CSM provides excellent long-term tumor and symptom control without considerable permanent side effects. Thus, SRS should be considered when counseling patients suffering from CSM.

Radiomic analysis of planning computed tomograms for predicting radiation-induced lung injury and outcome in lung cancer patients treated with robotic stereotactic body radiation therapy.

OBJECTIVES: To predict radiation-induced lung injury and outcome in non-small cell lung cancer (NSCLC) patients treated with robotic stereotactic body radiation therapy (SBRT) from radiomic features of the primary tumor. METHODS: In all, 110 patients with primary stage I/IIa NSCLC were analyzed for local control (LC), disease-free survival (DFS), overall survival (OS) and development of local lung injury up to fibrosis (LF). First-order (histogram), second-order (GLCM, Gray Level Co-occurrence Matrix) and shape-related radiomic features were determined from the unprocessed or filtered planning CT images of the gross tumor volume (GTV), subjected to LASSO (Least Absolute Shrinkage and Selection Operator) regularization and used to construct continuous and dichotomous risk scores for each endpoint. RESULTS: Continuous scores comprising 1-5 histogram or GLCM features had a significant (p = 0.0001-0.032) impact on all endpoints that was preserved in a multifactorial Cox regression analysis comprising additional clinical and dosimetric factors. At 36 months, LC did not differ between the dichotomous risk groups (93% vs. 85%, HR 0.892, 95%CI 0.222-3.590), while DFS (45% vs. 17%, p < 0.05, HR 0.457, 95%CI 0.240-0.868) and OS (80% vs. 37%, p < 0.001, HR 0.190, 95%CI 0.065-0.556) were significantly lower in the high-risk groups. Also, the frequency of LF differed significantly between the two risk groups (63% vs. 20% at 24 months, p < 0.001, HR 0.158, 95%CI 0.054-0.458). CONCLUSION: Radiomic analysis of the gross tumor volume may help to predict DFS and OS and the development of local lung fibrosis in early stage NSCLC patients treated with stereotactic radiotherapy.

Subcortical electrophysiological activity is detectable with high-density EEG source imaging.

Subcortical neuronal activity is highly relevant for mediating communication in large-scale brain networks. While electroencephalographic (EEG) recordings provide appropriate temporal resolution and coverage to study whole brain dynamics, the feasibility to detect subcortical signals is a matter of debate. Here, we investigate if scalp EEG can detect and correctly localize signals recorded with intracranial electrodes placed in the centromedial thalamus, and in the nucleus accumbens. Externalization of deep brain stimulation (DBS) electrodes, placed in these regions, provides the unique opportunity to record subcortical activity simultaneously with high-density (256 channel) scalp EEG. In three patients during rest with eyes closed, we found significant correlation between alpha envelopes derived from intracranial and EEG source reconstructed signals. Highest correlation was found for source signals in close proximity to the actual recording sites, given by the DBS electrode locations. Therefore, we present direct evidence that scalp EEG indeed can sense subcortical signals.

DiODe: Directional Orientation Detection of Segmented Deep Brain Stimulation Leads: A Sequential Algorithm Based on CT Imaging.

BACKGROUND: Directional deep brain stimulation (DBS) allows steering the stimulation in an axial direction which offers greater flexibility in programming. However, accurate anatomical visualization of the lead orientation is required for interpreting the observed stimulation effects and to guide programming. OBJECTIVES: In this study we aimed to develop and test an accurate and robust algorithm for determining the orientation of segmented electrodes based on standard postoperative CT imaging used in DBS. METHODS: Orientation angles of directional leads (CartesiaTM; Boston Scientific, Marlborough, MA, USA) were determined using CT imaging. Therefore, a sequential algorithm was developed that quantitatively compares the similarity of the observed CT artifacts with calculated artifact patterns based on the lead's orientation marker and a geometric model of the segmented electrodes. Measurements of seven ground truth phantoms and three leads with 60 different configurations of lead implantation and orientation angles were analyzed for validation. RESULTS: The accuracy of the determined electrode orientation angles was -0.6 ± 1.5° (range: -5.4 to 4.2°). This accuracy proved to be sufficiently high to resolve even subtle differences between individual leads. CONCLUSIONS: The presented algorithm is user independent and provides highly accurate results for the orientation of the segmented electrodes for all angular constellations that typically occur in clinical cases.

Acoustic Neuroma Treated with Stereotactic Radiosurgery: Follow-up of 335 Patients.

OBJECTIVE: To determine the clinical and radiologic outcome of patients with acoustic neuroma (AN) treated with linear accelerator (LINAC) or CyberKnife-based stereotactic radiosurgery with respect to tumor control, preservation of serviceable hearing, and toxicity. METHODS: A retrospective monocentric analysis including all patients who underwent single-fraction LINAC- or CyberKnife-based radiosurgery for AN between 1991 and 2015. Patient data were analyzed in terms of radiologic and clinical tumor control (no further intervention needed), treatment-related complications, preservation of serviceable hearing, and objectified hearing loss using pure tone average levels. RESULTS: We included 335 patients (median age 58.2 years, treated either by LINAC-based [n = 270] or CyberKnife [n = 65] stereotactic radiosurgery). The median tumor volume was 1.1 mL (0.1-23.7 mL). The median radiation dose was 12 Gy (LINAC 12 Gy, 11-20 Gy; CyberKnife 13 Gy, 12-13 Gy) at an isodose level of 71.7% (LINAC 68.3%, 31.9%-86.2%; CyberKnife 80%, 65%-81%). The median follow-up was 30 months (LINAC 43 months, 2-224 months; CyberKnife 13 months, 4-37 months). Clinical tumor control was 98%, 89%, and 88% at 2, 5, and 10 years. The objective actuarial hearing preservation rate was 89%, 80%, and 55% at 1, 2, and 5 years. New symptoms were observed in 11.3% and classified as Common Terminology Criteria for Adverse Events grade 1/2, apart from 4 patients (1.2%), who developed Common Terminology Criteria for Adverse Events grade 3. CONCLUSIONS: Our study shows that in AN, high tumor control and considerable hearing preservation rates can be achieved by single-dose radiosurgery at low toxicity rates, resulting in a positive impact on long-term clinical outcome.

Radiotoxicity in robotic radiosurgery: proposing a new quality index for optimizing the treatment planning of brain metastases.

BACKGROUND: As irradiated brain volume at 12 Gy (V12) is a predictor for radionecrosis, the purpose of the study was to develop a model for Cyberknife (CK) plans that is able to predict the lowest achievable V12 at a given tumor size and prescription dose (PD), and to suggest a new quality index regarding V12 for optimizing the treatment planning of brain metastases. METHOD: In our model V12 was approximated as a spherical shell around the tumor volume. The radial distance between tumor surface and the 12 Gy isodose line was calculated using an approximation of the mean dose gradient in that area. Assuming a radially symmetrical irradiation from the upper half space, the dose distribution is given by the superposition of single fields. The dose profiles of a single field were derived by the measured off-center ratios (OCR) of the CK system. Using the calculated gradients of the sum dose profiles, minimal-V12 was estimated for different tumor sizes. The model calculation was tested using a phantom dataset and retrospectively applied on clinical cases. RESULTS: Our model allows the prediction of a best-case scenario for V12 at a given tumor size and PD which was confirmed by the results of the isocentric phantom plans. The results of the non-isocentric phantom plans showed that an optimization of coverage caused an increase in V12. This was in accordance with the results of the retrospective analysis. V12 s of the clinical cases were on average twice that of the predicted model calculation. A good agreement was achieved for plans with an optimal conformity index (nCI). Re-planning of cases with high V12 showed that lower values could be reached by selecting smaller collimators and by allowing a larger number of total MU and more MU per beam. CONCLUSIONS: V12 is a main parameter for assessing plan quality in terms of radiotoxicity. The index f12 defined as the ratio of V12 from the actual plan with the evaluated V12 from our model describes the conformity of an optimally possible V12 and thus can be used as a new quality index for optimizing treatment plans.

Determining the orientation angle of directional leads for deep brain stimulation using computed tomography and digital x-ray imaging: A phantom study.

PURPOSE: Orientating the angle of directional leads for deep brain stimulation (DBS) in an axial plane introduces a new degree of freedom that is indicated by embedded anisotropic directional markers. Our aim was to develop algorithms to determine lead orientation angles from computed tomography (CT) and stereotactic x-ray imaging using standard clinical protocols, and subsequently assess the accuracy of both methods. METHODS: In CT the anisotropic marker artifact was taken as a signature of the lead orientation angle and analyzed using discrete Fourier transform of circular intensity profiles. The orientation angle was determined from phase angles at a frequency 2/360° and corrected for aberrations at oblique leads. In x-ray imaging, frontal and lateral images were registered to stereotactic space and sub-images containing directional markers were extracted. These images were compared with projection images of an identically located virtual marker at different orientation angles. A similarity index was calculated and used to determine the lead orientation angle. Both methods were tested using epoxy phantoms containing directional leads (Cartesia™, Boston Scientific, Marlborough, USA) with known orientation. Anthropomorphic phantoms were used to compare both methods for DBS cases. RESULTS: Mean deviation between CT and x-ray was 1.5° ± 3.6° (range: -2.3° to 7.9°) for epoxy phantoms and 3.6° ± 7.1° (range: -5.6° to 14.6°) for anthropomorphic phantoms. After correction for imperfections in the epoxy phantoms, the mean deviation from ground truth was 0.0° ± 5.0° (range: -12° to 14°) for x-ray. For CT the results depended on the polar angle of the lead in the scanner. Mean deviation was -0.3° ± 1.9° (range: -4.6° to 6.6°) or 1.6° ± 8.9° (range: -23° to 34°) for polar angles ≤ 40° or > 40°. CONCLUSIONS: The results show that both imaging modalities can be used to determine lead orientation angles with high accuracy. CT is superior to x-ray imaging, but oblique leads (polar angle > 40°) show limited precision due to the current design of the directional marker.

Probabilistic mapping of deep brain stimulation effects in essential tremor.

OBJECTIVE: To create probabilistic stimulation maps (PSMs) of deep brain stimulation (DBS) effects on tremor suppression and stimulation-induced side-effects in patients with essential tremor (ET). METHOD: Monopolar reviews from 16 ET-patients which consisted of over 600 stimulation settings were used to create PSMs. A spherical model of the volume of neural activation was used to estimate the spatial extent of DBS for each setting. All data was pooled and voxel-wise statistical analysis as well as nonparametric permutation testing was used to confirm the validity of the PSMs. RESULTS: PSMs showed tremor suppression to be more pronounced by stimulation in the zona incerta (ZI) than in the ventral intermediate nucleus (VIM). Paresthesias and dizziness were most commonly associated with stimulation in the ZI and surrounding thalamic nuclei. DISCUSSION: Our results support the assumption, that the ZI might be a very effective target for tremor suppression. However stimulation inside the ZI and in its close vicinity was also related to the occurrence of stimulation-induced side-effects, so it remains unclear whether the VIM or the ZI is the overall better target. The study demonstrates the use of PSMs for target selection and evaluation. While their accuracy has to be carefully discussed, they can improve the understanding of DBS effects and can be of use for other DBS targets in the therapy of neurological or psychiatric disorders as well. Furthermore they provide a priori information about expected DBS effects in a certain region and might be helpful to clinicians in programming DBS devices in the future.

Stereotactic intracavitary brachytherapy with P-32 for cystic craniopharyngiomas in children.

PURPOSE: Although microsurgery remains the first-line treatment, gross total resection of cystic craniopharyngeomas (CP) is associated with significant morbidity and mortality and the addition of external irradiation to subtotal resection proves to achieve similar tumor control. However, concern regarding long-term morbidity associated with external irradiation in children still remains. With this retrospective analysis, the authors emphasize intracavitary brachytherapy using phosphorus-32 (P-32) as a treatment option for children with cystic CP. PATIENTS AND METHODS: Between 1992 and 2009, 17 children (median age 15.4 years; range 7-18 years) with cystic CP underwent intracavitary brachytherapy using P-32. Eleven patients were treated for recurrent tumor cysts; 6 patients were treated primarily. MR imaging revealed solitary cysts in 7 patients; 10 patients had mixed solid-cystic lesions (median tumor volume 11.1 ml; range 0.5-78.9 ml). The median follow-up time was 61.9 months (range 16.9-196.6 months). RESULTS: Local cyst control could be achieved in 14 patients (82 %). Three patients showed progression of the treated cystic formation (in-field progression) after a median time of 8.3 months (range 5.3-10.3 months), which led to subsequent interventions. The development of new, defined cysts and progression of solid tumor parts (out-of-field progression) occurred in 5 patients and led to additional interventions in 4 cases. There was neither surgery-related permanent morbidity nor mortality in this study. The overall progression-free survival was 75, 63, and 52 % after 1, 3, and 5 years, respectively. CONCLUSION: Intracavitary brachytherapy using P-32 represents a safe and effective treatment option for children harboring cystic CP, even as primary treatment. However, P-32 does not clearly affect growth of solid tumor parts or the development of new cystic formations.

Stereotactic LINAC radiosurgery for the treatment of typical intracranial meningiomas. Efficacy and safety after a follow-up of over 12 years.

PURPOSE: The efficacy and safety of stereotactic radiosurgery (SRS) for treatment of intracranial meningiomas has been demonstrated in numerous studies with short- and intermediate-term follow-up. In this retrospective single-center study, we present long-term outcomes of SRS performed with a linear accelerator (LINAC) for typical intracranial meningiomas. PATIENTS AND METHODS: Between August 1990 and December 2007, 148 patients with 168 typical intracranial meningiomas were treated with stereotactic LINAC-SRS, either as primary treatment or after microsurgical resection. A median tumor surface dose of 12 Gy (range 7-20 Gy) and a median maximum dose of 24.1 Gy (range 11.3-58.6 Gy) was applied. The median target volume was 4.7 ml (range 0.2-32.8 ml, SD ± 4.8 ml). RESULTS: Overall mean radiological follow-up was 12.6 years. Tumor shrinkage was seen in 75 (44.6 %) and stable disease in 85 (50.6 %) cases. Eight of 168 meningiomas (4.8 %) showed local tumor progression. The tumor control rate (TCR) after 5, 10, and 15 years was 93.6 % at each time point, and the progression-free survival (PSF) rates were 92, 89, and 89 %, respectively. The neurological symptoms existing prior to LINAC-SRS improved in 77 patients (59.7 %), remained unchanged in 42 (32.6 %), and deteriorated in 10 (7.8 %) patients. CONCLUSION: Our study emphasizes the efficacy of LINAC-SRS for de novo, residual and recurrent typical intracranial meningiomas. A high long-term local TCR with a low morbidity rate could be achieved. LINAC-SRS should thus be considered as a primary treatment option, as one arm of a combined treatment approach for incompletely resected meningiomas, or as a salvage therapy for recurrences.