General Algorithm Applicability in Determining DBS Lead Orientation: Adapting 2D and 3D X-Ray Techniques for SenSightTM Leads.

INTRODUCTION: With recent advancements in deep brain stimulation (DBS), directional leads featuring segmented contacts have been introduced, allowing for targeted stimulation of specific brain regions. Given that manufacturers employ diverse markers for lead orientation, our investigation focuses on the adaptability of the 2017 techniques proposed by the Cologne research group for lead orientation determination. METHODS: We tailored the two separate 2D and 3D X-ray-based techniques published in 2017 and originally developed for C-shaped markers, to the dual-marker of the Medtronic SenSight™ lead. In a retrospective patient study, we evaluated their feasibility and consistency by comparing the degree of agreement between the two methods. RESULTS: The Bland-Altman plot showed favorable concordance without any noticeable systematic errors. The mean difference was 0.79°, with limits of agreement spanning from 21.4° to -19.8°. The algorithms demonstrated high reliability, evidenced by an intraclass correlation coefficient of 0.99 (p < 0.001). CONCLUSION: The 2D and 3D algorithms, initially formulated for discerning the circular orientation of a C-shaped marker, were adapted to the marker of the Medtronic SenSight™ lead. Statistical analyses revealed a significant level of agreement between the two methods. Our findings highlight the adaptability of these algorithms to different markers, achievable through both low-dose intraoperative 2D X-ray imaging and standard CT imaging.

Pseudoprogression of Vestibular Schwannoma after Stereotactic Radiosurgery with Cyberknife®: Proposal for New Response Criteria.

(1) Background: Transient increase in volume of vestibular schwannomas (VS) after stereotactic radiosurgery (SRS) is common and complicates differentiation between treatment-related changes (pseudoprogression, PP) and tumor recurrence (progressive disease, PD). (2) Methods: Patients with unilateral VS (n = 63) underwent single fraction robotic-guided SRS. Volume changes were classified according to existing RANO criteria. A new response type, PP, with a >20% transient increase in volume was defined and divided into early (within the first 12 months) and late (>12 months) occurrence. (3) Results: The median age was 56 (range: 20-82) years, the median initial tumor volume was 1.5 (range: 0.1-8.6) cm3. The median radiological and clinical follow-up time was 66 (range: 24-103) months. Partial response was observed in 36% (n = 23), stable disease in 35% (n = 22) and PP in 29% (n = 18) of patients. The latter occurred early (16%, n = 10) or late (13%, n = 8). Using these criteria, no case of PD was observed. (4) Conclusion: Any volume increase after SRS for vs. assumed to be PD turned out to be early or late PP. Therefore, we propose modifying RANO criteria for SRS of VS, which may affect the management of vs. during follow-up in favor of further observation.

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.

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.

DiODe v2: Unambiguous and Fully-Automated Detection of Directional DBS Lead Orientation.

Directional deep brain stimulation (DBS) leads are now widely used, but the orientation of directional leads needs to be taken into account when relating DBS to neuroanatomy. Methods that can reliably and unambiguously determine the orientation of directional DBS leads are needed. In this study, we provide an enhanced algorithm that determines the orientation of directional DBS leads from postoperative CT scans. To resolve the ambiguity of symmetric CT artifacts, which in the past, limited the orientation detection to two possible solutions, we retrospectively evaluated four different methods in 150 Cartesia™ directional leads, for which the true solution was known from additional X-ray images. The method based on shifts of the center of mass (COM) of the directional marker compared to its expected geometric center correctly resolved the ambiguity in 100% of cases. In conclusion, the DiODe v2 algorithm provides an open-source, fully automated solution for determining the orientation of directional DBS leads.

Frame-based stereotactic biopsy of deep-seated and midline structures in 511 procedures: feasibility, risk profile, and diagnostic yield.

OBJECTIVES: We evaluated the feasibility, safety, and diagnostic yield of frame-based stereotactic biopsies (SB) in lesions located in deep-seated and midline structures of the brain to analyze these parameters in comparison to other brain areas. PATIENTS AND METHODS: In a retrospective, tertiary care single-center analysis, we identified all patients who received SB for lesions localized in deep-seated and midline structures (corpus callosum, basal ganglia, pineal region, sella, thalamus, and brainstem) between January 1996 and June 2015. Study participants were between 1 and 82 years. We evaluated the feasibility, procedural complications (mortality, transient and permanent morbidity), and diagnostic yield. We further performed a risk analysis of factors influencing the latter parameters. Chi-square test, Student t test, and Mann-Whitney rank-sum test were used for statistical analysis. RESULTS: Four hundred eighty-nine patients receiving 511 SB procedures (median age 48.5 years, range 1-82; median Karnofsky Performance Score 80%, range 50-100%, 43.8% female/56.2% male) were identified. Lesions were localized in the corpus callosum (29.5%), basal ganglia (17.0%), pineal region (11.5%), sella (7.8%), thalamus (4.3%), brainstem (28.8%), and others (1.1%). Procedure-related mortality was 0%, and permanent morbidity was 0.4%. Transient morbidity was 9.6%. Histological diagnosis was possible in 99.2% (low-grade gliomas 16.2%, high-grade gliomas 40.3%, other tumors in 27.8%, no neoplastic lesions 14.5%, no definitive histological diagnosis 0.8%). Only the pons location correlated significantly with transient morbidity (p < 0.001). CONCLUSION: In experienced centers, frame-based stereotactic biopsy is a safe diagnostic tool with a high diagnostic yield also for deep-seated and midline lesions.

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.

Reduction of Artifacts Caused by Deep Brain Stimulating Electrodes in Cranial Computed Tomography Imaging by Means of Virtual Monoenergetic Images, Metal Artifact Reduction Algorithms, and Their Combination.

OBJECTIVES: The aim of this study was to evaluate the reduction of artifacts from deep brain stimulation electrodes (DBS) using an iterative metal artifact reduction algorithm (O-MAR), virtual monoenergetic images (VMI), and both in combination in postoperative spectral detector computed tomography using a dual-layer detector (spectral detector computed tomography [SDCT]) of the head. MATERIAL AND METHODS: Nonanthropomorphic phantoms with different DBS leads were examined on SDCT; in 1 phantom periprocedural bleeding was simulated. A total of 20 patients who underwent SDCT after DBS implantation between October 2016 and April 2017 were included in this institutional review board-approved retrospective study. Images were reconstructed using standard-of-care iterative reconstruction (CI) and VMI, each with and without O-MAR processing (IR and MAR). Artifacts were quantified by determining the percentage integrity uniformity in an annular region of 1.4 cm around the DBS lead; a percentage integrity uniformity of 100% indicates the absence of artifacts. In phantoms, conspicuity of blood was determined on a binary scale, whereas in patients, image quality, DBS lead assessment, and extent of artifact reduction were assessed on Likert scales by 2 radiologists. Statistical significance was assessed using analysis of variance and Wilcoxon tests; sensitivity and specificity were calculated. RESULTS: The O-MAR processing significantly decreased artifacts in phantom and patients (P ≤ 0.05), whereas VMI did not reduce artifact burden compared with corresponding CI (P > 0.05): for example, CI-IR/MAR and 200 keV-IR/MAR for patients: 76.3%/90.7% and 75.9%/91.2%, respectively. Qualitatively, overall image quality was not improved (P > 0.05) and MAR improved DBS assessment (CI-IR/MAR: 2 [1-3]/3 [2-4]; P ≤ 0.05) and reduced artifacts significantly (P ≤ 0.05). The O-MAR processing increased sensitivity for bleeding by 160%. In some cases, new artifacts were induced through O-MAR processing, none of which impaired diagnostic image assessment. DISCUSSION: The investigated O-MAR algorithm reduces artifacts from DBS electrodes and should be used in the assessment of postoperative patients; however, combination with VMI does not provide an additional benefit.

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.

Long-term follow-up after stereotactic radiosurgery of intracanalicular acoustic neurinoma.

BACKGROUND: The management of solely intracanalicular acoustic neurinoma (iAN) includes observation, microsurgical resection and radiation therapy. Treatment goals are long-term tumor control, hearing preservation and concurrently low side-effects. Stereotactic radiosurgery (SRS) has evolved as an alternative first-line treatment for small AN. Here we report about the long-term follow-up of a unique cohort of patients with iAN after LINAC or Cyberknife® based SRS. METHODS: In this single center retrospective analysis, we included all patients with iAN who underwent single session LINAC or Cyberknife® based SRS between 1993 and 2015, and who had a minimum follow-up period of six weeks. Patient data were analyzed in terms of radiological and clinical tumor control (no further treatment necessary), subjective preservation of serviceable hearing, objective change in pure tone averages (PTA), and adverse events rated by the Common Terminology Criteria for Adverse Events (CTCAE; v4.03). RESULTS: Forty-nine patients (f/m = 21/28, median age 54 ± 12, range 20-77 years) were identified. Mean tumor volumes were 0.24 ± 0.12 cm3 (range, 0.1-0.68 cm3), the mean marginal dose was 12.6 ± 0.6 Gy (range, 11.0-14.0 Gy) and the prescription isodose was 75 ± 7.4% (range, 47-86%). Mean follow-up time was 65 months (range, 4-239 months). Radiological tumor control was 100% during further follow-up. 17 (35%) out of 49 patients had lost serviceable hearing prior to SRS. Those with preserved serviceable hearing remained stable in 78% (n = 25/32) at the last follow-up (LFU). The median PTA (n = 16) increased from 25.6 dB prior to SRS to 43.8 dB at LFU. Mild adverse events were observed temporarily in two patients (4%): one with CTCAE grade 1 facial nerve disorder after 3 months, resolving three months later, and one with CTCAE grade 2 facial muscle weakness resolving after 12 months. Three patients described permanent mild symptoms CTCAE grade 1 without limiting daily life (facial weakness n = 1, vertigo n = 2). CONCLUSION: SRS for iAN shows long-term reliable tumor control with a high rate of hearing preservation without considerable permanent side effects, and can be proposed as a safe and effective treatment alternative to microsurgical resection.

MRI phantoms - are there alternatives to agar?

The suitability of different gelling agents as MRI phantoms was evaluated in terms of homogeneity, gel stability and reproducibility. Time and effort for preparation were also taken into account. The relaxation times of various gel compositions were estimated. Carbomer-980 and Carbopol-974P were determined to be promising novel phantom materials. These gelling agents are readily available, inexpensive and easy to handle given that thermal treatment is not required. Furthermore, the viscoelasticity of their polymer network is pH-dependent. With such characteristics, it was even possible to embed sensitive objects and retrieve them after testing. This was demonstrated with a fiber phantom for Diffusion Weighted MRI applications. Since Carbomer-980 and Carbopol-974P are non-hazardous, they are also suitable for multimodal setups (e.g., MRI as well as ultrasonic imaging).

Comparison of isotopic substitution methods for equilibrium and t-jump infrared studies of beta-hairpin peptide conformation.

Laser induced temperature jump (T-jump) relaxation kinetics were measured with infrared absorbance (IR) detection for a set of beta-hairpin peptides, related to the Trpzip2 hairpin, but containing single isotopic labels, (13)C on the amide C horizontal lineO of selected residues both in the center of the strands and at the terminal regions of the hairpin. Variations in the behavior of single labeled peptides are compared to those previously reported for double labeled variants. Although single labels do not result in spectral intensity enhancement, as seen for cross-strand labeling, the IR frequency shifts are still diagnostic of hairpin unfolding. If C horizontal lineO's in the beta-strand portion of the hairpin (between the Trp residues) are labeled, the dynamic behavior of the local modes is similar to the results obtained with double labels in terms of relaxation time and activation energy and closely tracks the kinetics of the beta-strand components. This implies that either property, local secondary structure (change of varphi,psi), or cross-strand coupling enabled by strand formation and H-bonding relaxes with the same kinetic mechanism. Single labeled residues on the terminal positions have a different behavior and are less able to be detected due to overlap with the (12)C components, in contrast to double labels involving these positions, which are enhanced due to coupling. DFT-based spectral simulations that use the NMR structure of Trpzip2C indicate that the single labeled peptides should have roughly equivalent (12)C bands but the (13)C mode frequencies will vary with sequence position. Effective solvent corrections using COSMO yield significant changes in the frequencies but not in the relative isotope shifts obtained in our calculated spectra. Sequence positional dependence of labels is shown to be more discriminatory for kinetics changes than for thermodynamic variations.