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Radiation sparing of cerebral cortex in brain tumor patients using quantitative neuroimaging.

ABSTRACT: Neurocognitive decline in brain tumor patients treated with radiotherapy (RT) may be linked to cortical atrophy. We developed models to determine radiation treatment-planning objectives for cortex, which were tested on a sample population to identify the dosimetric cost of cortical sparing.The relationship between the probability of cortical atrophy in fifteen high-grade glioma patients at 1-year post-RT and radiation dose was fit using logistic mixed effects modeling. Cortical sparing was implemented using two strategies: region-specific sparing using model parameters, and non-specific sparing of all normal brain tissue.A dose threshold of 28.6 Gy was found to result in a 20% probability of severe atrophy. Average cortical sparing at 30 Gy was greater for region-specific dose avoidance (4.6%) compared to non-specific (3.6%). Cortical sparing resulted in an increase in heterogeneity index of the planning target volume (PTV) with an average increase of 1.9% (region-specific) and 0.9% (non-specific).We found RT doses above 28.6 Gy resulted in a greater than 20% probability of cortical atrophy. Cortical sparing can be achieved using region-specific or non-specific dose avoidance strategies at the cost of an increase in the dose heterogeneity of the PTV.

SUBMITTER: Karunamuni RA

PROVIDER: S-EPMC4764402 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Radiation sparing of cerebral cortex in brain tumor patients using quantitative neuroimaging.

Karunamuni Roshan A RA Moore Kevin L KL Seibert Tyler M TM Li Nan N White Nathan S NS Bartsch Hauke H Carmona Ruben R Marshall Deborah D McDonald Carrie R CR Farid Nikdokht N Krishnan Anithapriya A Kuperman Joshua J Mell Loren K LK Brewer James J Dale Anders M AM Moiseenko Vitali V Hattangadi-Gluth Jona A JA

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 20160121 1

<h4>Background and purpose</h4>Neurocognitive decline in brain tumor patients treated with radiotherapy (RT) may be linked to cortical atrophy. We developed models to determine radiation treatment-planning objectives for cortex, which were tested on a sample population to identify the dosimetric cost of cortical sparing.<h4>Material and methods</h4>The relationship between the probability of cortical atrophy in fifteen high-grade glioma patients at 1-year post-RT and radiation dose was fit using ...[more]

PMID: 26806266

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Project description:Radiation therapy is widely used for the treatment of brain tumors and may result in cellular, vascular and axonal injury and further behavioral deficits. The non-invasive longitudinal imaging assessment of brain injury caused by radiation therapy is important for determining patient prognoses. Several rodent studies have been performed using magnetic resonance imaging (MRI), but further studies in rabbits and large mammals with advanced magnetic resonance (MR) techniques are needed. Previously, we used diffusion tensor imaging (DTI) to evaluate radiation-induced rabbit brain injury. However, DTI is unable to resolve the complicated neural structure changes that are frequently observed during brain injury after radiation exposure. Generalized q-sampling imaging (GQI) is a more accurate and sophisticated diffusion MR approach that can extract additional information about the altered diffusion environments. Therefore, herein, a longitudinal study was performed that used GQI indices, including generalized fractional anisotropy (GFA), quantitative anisotropy (QA), and the isotropic value (ISO) of the orientation distribution function and DTI indices, including fractional anisotropy (FA) and mean diffusivity (MD) over a period of approximately half a year to observe long-term, radiation-induced changes in the different brain compartments of a rabbit model after a hemi-brain single dose (30 Gy) radiation exposure. We revealed that in the external capsule, the GFA right to left (R/L) ratio showed similar trends as the FA R/L ratio, but no clear trends in the remaining three brain compartments. Both the QA and ISO R/L ratios showed similar trends in the all four different compartments during the acute to early delayed post-irradiation phase, which could be explained and reflected the histopathological changes of the complicated dynamic interactions among astrogliosis, demyelination and vasogenic edema. We suggest that GQI is a promising non-invasive technique and as compared with DTI, it has better potential ability in detecting and monitoring the pathophysiological cascades in acute to early delayed radiation-induced brain injury by using clinical MR scanners.

Project description:Cortical thinning patterns in Alzheimer's disease (AD) have been widely reported through conventional regional analysis. In addition, the coordinated variance of cortical thickness in different brain regions has been investigated both at the individual and group network levels. In this study, we aim to investigate network architectural characteristics of a structural covariance network (SCN) in AD, and further to show that the structural covariance connectivity becomes disorganized across the brain regions in AD, while the normal control (NC) subjects maintain more clustered and consistent coordination in cortical atrophy variations. We generated SCNs directly from T1-weighted MR images of individual patients using surface-based cortical thickness data, with structural connectivity defined as similarity in cortical thickness within different brain regions. Individual SCNs were constructed using morphometric data from the Samsung Medical Center (SMC) dataset. The structural covariance connectivity showed higher clustering than randomly generated networks, as well as similar minimum path lengths, indicating that the SCNs are "small world." There were significant difference between NC and AD group in characteristic path lengths (z = -2.97, p < 0.01) and small-worldness values (z = 4.05, p < 0.01). Clustering coefficients in AD was smaller than that of NC but there was no significant difference (z = 1.81, not significant). We further observed that the AD patients had significantly disrupted structural connectivity. We also show that the coordinated variance of cortical thickness is distributed more randomly from one region to other regions in AD patients when compared to NC subjects. Our proposed SCN may provide surface-based measures for understanding interaction between two brain regions with co-atrophy of the cerebral cortex due to normal aging or AD. We applied our method to the AD Neuroimaging Initiative (ADNI) data to show consistency in results with the SMC dataset.

Project description:The purpose of this study was to retrospectively investigate the accuracy, plan quality, and efficiency of using intensity-modulated arc therapy (IMAT) for whole brain radiotherapy (WBRT) patients with sparing not only the hippocampus (following RTOG 0933 compliance criteria) but also other organs at risk (OARs). A total of 10 patients previously treated with nonconformal opposed laterals whole-brain radiotherapy (NC-WBRT) were retrospectively replanned for hippocampal sparing using IMAT treatment planning. The hippocampus was volumetrically contoured on fused diagnostic T1-weighted MRI with planning CT images and hippocampus avoidance zone (HAZ) was generated using a 5 mm uniform margin around the hippocampus. Both hippocampi were defined as one paired organ. Whole brain tissue minus HAZ was defined as the whole-brain planning target volume (WB-PTV). Highly conformal IMAT plans were generated in the Eclipse treatment planning system for Novalis TX linear accelerator consisting of high-definition multileaf collimators (HD-MLCs: 2.5 mm leaf width at isocenter) and 6 MV beam for a prescription dose of 30 Gy in 10 fractions following RTOG 0933 dosimetric criteria. Two full coplanar arcs with orbits avoidance sectors were used. In addition to RTOG criteria, doses to other organs at risk (OARs), such as parotid glands, cochlea, external/middle ear canals, skin, scalp, optic pathways, brainstem, and eyes/lens, were also evaluated. Subsequently, dose delivery efficiency and accuracy of each IMAT plan was assessed by delivering quality assurance (QA) plans with a MapCHECK device, recording actual beam-on time and measuring planed vs. measured dose agreement using a gamma index. On IMAT plans, following RTOG 0933 dosimetric criteria, the maximum dose to WB-PTV, mean WB-PTV D2%, and mean WB-PTV D98% were 34.9 ± 0.3 Gy, 33.2 ± 0.4 Gy, and 26.0± 0.4Gy, respectively. Accordingly, WB-PTV received the prescription dose of 30Gy and mean V30 was 90.5% ± 0.5%. The D100%, and mean and maximum doses to hippocampus were 8.4 ± 0.3 Gy, 11.2 ± 0.3 Gy, and 15.6 ± 0.4 Gy, on average, respectively. The mean values of homogeneity index (HI) and conformity index (CI) were 0.23 ± 0.02 and 0.96 ± 0.02, respectively. The maximum point dose to WB-PTV was 35.3 Gy, well below the optic pathway tolerance of 37.5 Gy. In addition, compared to NC-WBRT, dose reduction of mean and maximum of parotid glands from IMAT were 65% and 50%, respectively. Ear canals mean and maximum doses were reduced by 26% and 12%, and mean and maximum scalp doses were reduced by 9 Gy (32%) and 2 Gy (6%), on average, respectively. The mean dose to skin was 9.7 Gy with IMAT plans compared to 16 Gy with conventional NC-WBRT, demonstrating that absolute reduction of skin dose by a factor of 2. The mean values of the total number of monitor units (MUs) and actual beam on time were 719 ± 44 and 2.34 ± 0.14 min, respectively. The accuracy of IMAT QA plan delivery was (98.1 ± 0.8) %, on average, with a 3%/3 mm gamma index passing rate criteria. All of these plans were considered clinically acceptable per RTOG 0933 criteria. IMAT planning provided highly conformal and homogenous plan with a fast and effective treatment option for WBRT patients, sparing not only hippocampi but also other OARs, which could potentially result in an additional improvement of the quality life (QoL). In the future, we plan to evaluate the clinical potential of IMAT planning and treatment option with hippocampal and other OARs avoidance in our patient's cohort and asses the QoL of the WBRT patients, as well as simultaneous integrated boost (SIB) for the brain metastases diseases.

Project description:Purpose and objectivesNeurologic deficits after brain radiation therapy (RT) typically involve decline in higher-order cognitive functions such as attention and memory rather than sensory defects or paralysis. We sought to determine whether areas of the cortex critical to cognition are selectively vulnerable to radiation dose-dependent atrophy.Methods and materialsWe measured change in cortical thickness in 54 primary brain tumor patients who underwent fractionated, partial brain RT. The study patients underwent high-resolution, volumetric magnetic resonance imaging (T1-weighted; T2 fluid-attenuated inversion recovery, FLAIR) before RT and 1 year afterward. Semiautomated software was used to segment anatomic regions of the cerebral cortex for each patient. Cortical thickness was measured for each region before RT and 1 year afterward. Two higher-order cortical regions of interest (ROIs) were tested for association between radiation dose and cortical thinning: entorhinal (memory) and inferior parietal (attention/memory). For comparison, 2 primary cortex ROIs were also tested: pericalcarine (vision) and paracentral lobule (somatosensory/motor). Linear mixed-effects analyses were used to test all other cortical regions for significant radiation dose-dependent thickness change. Statistical significance was set at α = 0.05 using 2-tailed tests.ResultsCortical atrophy was significantly associated with radiation dose in the entorhinal (P=.01) and inferior parietal ROIs (P=.02). By contrast, no significant radiation dose-dependent effect was found in the primary cortex ROIs (pericalcarine and paracentral lobule). In the whole-cortex analysis, 9 regions showed significant radiation dose-dependent atrophy, including areas responsible for memory, attention, and executive function (P≤.002).ConclusionsAreas of cerebral cortex important for higher-order cognition may be most vulnerable to radiation-related atrophy. This is consistent with clinical observations that brain radiation patients experience deficits in domains of memory, executive function, and attention. Correlations of regional cortical atrophy with domain-specific cognitive functioning in prospective trials are warranted.

Project description:PurposeWe used quantitative magnetic resonance imaging to prospectively analyze the association between microstructural damage to memory-associated structures within the medial temporal lobe and longitudinal memory performance after brain radiation therapy (RT).Methods and materialsPatients with a primary brain tumor receiving fractionated brain RT were enrolled on a prospective trial (n = 27). Patients underwent high-resolution volumetric brain magnetic resonance imaging, diffusion-weighted imaging, and neurocognitive testing before and 3, 6, and 12 months post-RT. Medial temporal lobe regions (hippocampus; entorhinal, parahippocampal, and temporal pole white matter [WM]) were autosegmented, quantifying volume and diffusion biomarkers of WM integrity (mean diffusivity [MD]; fractional anisotropy [FA]). Reliable change indices measured changes in verbal (Hopkins Verbal Learning Test-Revised) and visuospatial (Brief Visuospatial Memory Test-Revised [BVMT-R]) memory. Linear mixed-effects models assessed longitudinal associations between imaging parameters and memory.ResultsVisuospatial memory significantly declined at 6 months post-RT (mean reliable change indices, -1.3; P = .012). Concurrent chemotherapy and seizures trended toward a significant association with greater decline in visuospatial memory (P = .053 and P = .054, respectively). Higher mean dose to the left temporal pole WM was significantly associated with decreased FA (r = -0.667; P = .002). Over all time points, smaller right hippocampal volume (P = .021), lower right entorhinal FA (P = .023), greater right entorhinal MD (P = .047), and greater temporal pole MD (BVMT-R total recall, P = .003; BVMT-R delayed recall, P = .042) were associated with worse visuospatial memory. The interaction between right entorhinal MD (BVMT-R total recall, P = .021; BVMT-R delayed recall, P = .004) and temporal pole FA (BVMT-R delayed recall, P = .024) significantly predicted visuospatial memory performance.ConclusionsBrain tumor patients exhibited visuospatial memory decline post-RT. Microstructural damage to critical memory regions, including the hippocampus and medial temporal lobe WM, were associated with post-RT memory decline. The integrity of medial temporal lobe structures is critical to memory performance post-RT, representing possible avoidance targets for memory preservation.

Dataset Information

Radiation sparing of cerebral cortex in brain tumor patients using quantitative neuroimaging.

Publications

Radiation sparing of cerebral cortex in brain tumor patients using quantitative neuroimaging.

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