Connectomic Basis for Tremor Control in Stereotactic Radiosurgical Thalamotomy.

BACKGROUND AND PURPOSE: Given the increased use of stereotactic radiosurgical thalamotomy and other ablative therapies for tremor, new biomarkers are needed to improve outcomes. Using resting-state fMRI and MR tractography, we hypothesized that a "connectome fingerprint" can predict tremor outcomes and potentially serve as a targeting biomarker for stereotactic radiosurgical thalamotomy. MATERIALS AND METHODS: We evaluated 27 patients who underwent unilateral stereotactic radiosurgical thalamotomy for essential tremor or tremor-predominant Parkinson disease. Percentage postoperative improvement in the contralateral limb Fahn-Tolosa-Marin Clinical Tremor Rating Scale (TRS) was the primary end point. Connectome-style resting-state fMRI and MR tractography were performed before stereotactic radiosurgery. Using the final lesion volume as a seed, "connectivity fingerprints" representing ideal connectivity maps were generated as whole-brain R-maps using a voxelwise nonparametric Spearman correlation. A leave-one-out cross-validation was performed using the generated R-maps. RESULTS: The mean improvement in the contralateral tremor score was 55.1% (SD, 38.9%) at a mean follow-up of 10.0 (SD, 5.0) months. Structural connectivity correlated with contralateral TRS improvement (r = 0.52; P = .006) and explained 27.0% of the variance in outcome. Functional connectivity correlated with contralateral TRS improvement (r = 0.50; P = .008) and explained 25.0% of the variance in outcome. Nodes most correlated with tremor improvement corresponded to areas of known network dysfunction in tremor, including the cerebello-thalamo-cortical pathway and the primary and extrastriate visual cortices. CONCLUSIONS: Stereotactic radiosurgical targets with a distinct connectivity profile predict improvement in tremor after treatment. Such connectomic fingerprints show promise for developing patient-specific biomarkers to guide therapy with stereotactic radiosurgical thalamotomy.

Implementation of talairach atlas based automated brain segmentation for radiation therapy dosimetry.

Radiotherapy for brain cancer inevitably results in irradiation of uninvolved brain. While it has been demonstrated that irradiation of the brain can result in cognitive deficits, dose-volume relationships are not well established. There is little work correlating a particular cognitive deficit with dose received by the region of the brain responsible for the specific cognitive function. One obstacle to such studies is that identification of brain anatomy is both labor intensive and dependent on the individual performing the segmentation. Automatic segmentation has the potential to be both efficient and consistent. Brains2 is a software package developed by the University of Iowa for MRI volumetric studies. It utilizes MR images, the Talairach atlas, and an artificial neural network (ANN) to segment brain images into substructures in a standardized manner. We have developed a software package, Brains2DICOM, that converts the regions of interest identified by Brains2 into a DICOM radiotherapy structure set. The structure set can be imported into a treatment planning system for dosimetry. We demonstrated the utility of Brains2DICOM using a test case, a 34-year-old man with diffuse astrocytoma treated with three-dimensional conformal radiotherapy. Brains2 successfully applied the Talairach atlas to identify the right and left frontal, parietal, temporal, occipital, subcortical, and cerebellum regions. Brains2 was not successful in applying the ANN to identify small structures, such as the hippocampus and caudate. Further work is necessary to revise the ANN or to develop new methods for identification of small structures in the presence of disease and radiation induced changes. The segmented regions-of-interest were transferred to our commercial treatment planning system using DICOM and dose-volume histograms were constructed. This method will facilitate the acquisition of data necessary for the development of normal tissue complication probability (NTCP) models that assess the probability of cognitive complications secondary to radiotherapy for intracranial and head and neck neoplasms.

Effect of multileaf collimator leaf width on physical dose distributions in the treatment of CNS and head and neck neoplasms with intensity modulated radiation therapy.

The purpose of this work is to examine physical radiation dose differences between two multileaf collimator (MLC) leaf widths (5 and 10 mm) in the treatment of CNS and head and neck neoplasms with intensity modulated radiation therapy (IMRT). Three clinical patients with CNS tumors were planned with two different MLC leaf sizes, 5 and 10 mm, representing Varian-120 and Varian-80 Millennium multileaf collimators, respectively. Two sets of IMRT treatment plans were developed. The goal of the first set was radiation dose conformality in three dimensions. The goal for the second set was organ avoidance of a nearby critical structure while maintaining adequate coverage of the target volume. Treatment planning utilized the CadPlan/Helios system (Varian Medical Systems, Milpitas CA) for dynamic MLC treatment delivery. All beam parameters and optimization (cost function) parameters were identical for the 5 and 10 mm plans. For all cases the number of beams, gantry positions, and table positions were taken from clinically treated three-dimensional conformal radiotherapy plans. Conformality was measured by the ratio of the planning isodose volume to the target volume. Organ avoidance was measured by the volume of the critical structure receiving greater than 90% of the prescription dose (V(90)). For three patients with squamous cell carcinoma of the head and neck (T2-T4 N0-N2c M0) 5 and 10 mm leaf widths were compared for parotid preservation utilizing nine coplanar equally spaced beams delivering a simultaneous integrated boost. Because modest differences in physical dose to the parotid were detected, a NTCP model based upon the clinical parameters of Eisbruch et al. was then used for comparisons. The conformality improved in all three CNS cases for the 5 mm plans compared to the 10 mm plans. For the organ avoidance plans, V(90) also improved in two of the three cases when the 5 mm leaf width was utilized for IMRT treatment delivery. In the third case, both the 5 and 10 mm plans were able to spare the critical structure with none of the structure receiving more than 90% of the prescription dose, but in the moderate dose range, less dose was delivered to the critical structure with the 5 mm plan. For the head and neck cases both the 5 and 10 x 2.5 mm beamlets dMLC sliding window techniques spared the contralateral parotid gland while maintaining target volume coverage. The mean parotid dose was modestly lower with the smaller beamlet size (21.04 Gy v 22.36 Gy). The resulting average NTCP values were 13.72% for 10 mm dMLC and 8.24% for 5 mm dMLC. In conclusion, five mm leaf width results in an improvement in physical dose distribution over 10 mm leaf width that may be clinically relevant in some cases. These differences may be most pronounced for single fraction radiosurgery or in cases where the tolerance of the sensitive organ is less than or close to the target volume prescription.

Beam-commissioning methodology for a three-dimensional convolution/superposition photon dose algorithm.

Commissioning beam data for the convolution/superposition dose-calculation algorithm used in a commercial three-dimensional radiation treatment planning (3D RTP) system (PINNACLE(3), ADAC Laboratories, Milpitas, CA) can be difficult and time consuming. Sixteen adjustable parameters, as well as spectral weights representing a discrete energy spectrum, must be fit to sets of central-axis depth doses and off-axis profiles for a large number of field sizes. This paper presents the beam-commissioning methodology that we used to generate accurate beam models. The methodology is relatively rapid and provides physically reasonable values for beam parameters. The methodology was initiated by using vendor-provided automodeling software to generate a single set of beam parameters that gives an approximate fit to relative dose distributions for all beams, open and wedged, in a data set. A limited number of beam parameters were adjusted by small amounts to give accurate beam models for four open-beam field sizes and three wedged-beam field sizes. Beam parameters for other field sizes were interpolated and validated against measured beam data. Using this methodology, a complete set of beam parameters for a single energy can be generated and validated in approximately 40 h. The resulting parameter values yielded calculated relative doses that matched measured relative doses in a water phantom to within 0.5-1.0% along the central axis and 2% along off-axis beam profiles for field sizes from 4 cmx4 cm to the largest field size available. While the methodology presented is specific to the ADAC PINNACLE(3) treatment planning system, the approach should apply to other implementations of the dose model in other treatment planning system.