Adaptive control is reversed between hands after left hemisphere stroke and lost following right hemisphere stroke.

Human motor adaptability is of utmost utility after neurologic injury such as unilateral stroke. For successful adaptive control of movements, the nervous system must learn to correctly identify the source of a movement error and predictively compensate for this error. The current understanding is that in bimanual tasks, this process is flexible such that errors are assigned to, and compensated for, by the limb that is more likely to produce those errors. Here, we tested the flexibility of the error assignment process in right-handed chronic stroke survivors using a bimanual reaching task in which the hands jointly controlled a single cursor. We predicted that the nondominant left hand in neurotypical adults and the paretic hand in chronic stroke survivors will be more responsible for cursor errors and will compensate more within a trial and learn more from trial to trial. We found that in neurotypical adults, the nondominant left hand does compensate more than the right hand within a trial but learns less trial-to-trial. After a left hemisphere stroke, the paretic right hand compensates more than the nonparetic left hand within-trial but learns less trial-to-trial. After a right hemisphere stroke, the paretic left hand neither corrects more within-trial nor learns more trial-to-trial. Thus, adaptive control of visually guided bimanual reaching movements is reversed between hands after the left hemisphere stroke and lost following the right hemisphere stroke. These results indicate that responsibility assignment is not fully flexible but depends on a central mechanism that is lateralized to the right hemisphere.

Signals from Single-Opponent Cortical Cells in the Human cVEP.

We used the chromatic visual evoked potential (cVEP) to study responses in human visual cortex evoked by equiluminant color stimuli for 6 male and 11 female observers. Large-area, colored squares were used to stimulate Single-Opponent cells preferentially, and fine color-checkerboard stimuli were used to activate Double-Opponent responses preferentially. Stimuli were modulated along the following two directions in color space: (1) the cardinal direction, L-M or M-L of DKL (Derrington, Krauskopf, and Lennie) space; and (2) the line from the white point to the color of the Red LED in the display screen, which was approximately intermediate between the L-M and -S directions in DKL space in cone-contrast coordinates. The amplitudes of cVEPs to large squares were smaller than those to checkerboards, and the latency of the cVEP response to squares was significantly less than the checkerboard latency. The latency of cVEP responses to the squares varied little with cone-contrast unlike the steep reduction of latency with cone-contrast observed in responses to color checkerboard patterns. The dynamic differences between cVEPs to squares and checkerboards support the hypothesis that a distinct neuronal mechanism responded to squares: Single-Opponent cells. Response amplitude, latency, and transientness-and their dependence on cone-contrast-were similar in the responses in the L-M and Red color directions. The similarity supports the hypothesis that the Single-Opponent signals in the cVEP come from a distinct population of cells that receives subtractive inputs from L and M cones, either L-M or M-L.SIGNIFICANCE STATEMENT This article is about characterizing the visual behavior of a distinct population of neurons in the human visual cortex, the Single-Opponent color cells. Based on single-cell results in the visual cortex of macaque monkeys, we used large uniformly colored stimuli to isolate the responses of Single-Opponent cells in the chromatic visual evoked potential (cVEP) recorded on the scalp of human observers. VEP signals recorded under conditions believed to reveal Single-Opponent responses are small and transient. Their time course is relatively unaffected by cone-contrast, and they are relatively insensitive to stimulus modulation of short wavelength-sensitive S cones. Because Single-Opponent cells convey signals that can be used to judge the color of scene illumination, knowing their visual properties is important for understanding color vision.

Frequency-domain analysis of transient visual evoked potentials in schizophrenia.

PURPOSE: Frequency-domain measures were applied to characterize neural deficits in individuals with schizophrenia using transient visual evoked potentials (tVEP). These measures were compared with conventional time-domain measures to elucidate underlying neurophysiological mechanisms and examine the value of frequency analysis. METHODS: Four frequency bands of activity identified in previous work were explored with respect to magnitude (spectral power), timing (phase), a combined measure, magnitude-squared coherence (MSC), and compared to amplitudes and times of prominent deflections in the response. RESULTS: Band 2 power/MSC (14-28 Hz) captured the major deflections in the waveform and its power predicted N75-P100 amplitude for patients and controls. Band 3 power/MSC (30-40 Hz) correlated highly with the earliest deflection (P60-N75), reflecting input to primary visual cortex (V1) and produced the largest magnitude effect. Phase of the 24th harmonic component predicted P100 peak time for patients and controls and yielded the largest group difference. Cluster analyses including time- and frequency-domain measures identified subgroups of patients with differential neurophysiological effects. A small but significant difference in visual acuity was found between groups that appears to be neurally based: Acuity (range 0.63-1.6) was not correlated with any tVEP measures in controls nor with input timing to V1 (P60 peak time) in patients, but was correlated with later tVEP measures in patients. All but two of the patients were on antipsychotic medication: Medication level (chlorpromazine equivalents) was correlated negatively with tVEP time measures and positively with certain magnitude measures yielding responses similar to controls at high levels. CONCLUSIONS: Overall, frequency-domain measures were shown to be objective and recommended as an alternative to conventional, subjective time-domain measures for analyzing tVEPs and in distinguishing between groups (patients vs. controls and patient subgroups). The findings implicated a loss of excitatory input to V1 in schizophrenia. Acuity as measured in the current study reflected disease status, and medication level was associated with improved tVEP responses. These novel tVEP techniques may be useful in revealing neurophysiological processes affected in schizophrenia and as a clinical tool.

Contrast sensitivity deficits in schizophrenia: A psychophysical investigation.

Individuals with schizophrenia have problems with visual contrast processing. The current study investigated contrast sensitivity (CS) in schizophrenia/schizoaffective disorder to elucidate the underlying neural mechanisms affected by this disorder and to identify critical testing conditions that distinguish individuals with the disorder from healthy individuals. Principal component analysis was applied to the data (N = 143) to separate responses from distinct visual pathways. Participants were 68 patients and 75 age-similar controls. CS was obtained using a forced-choice psychophysical paradigm with grating patterns of low to high spatial frequency presented at short and long durations. Linear mixed-effects models were used to examine differences in log CS with respect to group, duration, and stimulus condition. Lower CSs were found in patients compared to controls over all stimulus conditions with the magnitude of deficits dependent on both spatial frequency and stimulus duration. Log CSs to low and high spatial frequencies loaded onto separate principal components, supporting the existence of two psychophysical mechanisms, transient and sustained. Critical conditions were identified to tap each mechanism. Visual acuity was correlated moderately with log CS to high, but not low, spatial frequencies, and deficits found for acuity and CS to moderate/high spatial frequencies (4-21 cycles/degree) appear to reflect dysfunction in the sustained mechanism. CS deficits found at the lowest spatial frequency tested (0.5 cycles/degree) appear to reflect dysfunction in the transient mechanism. Both types of CS deficits may have diagnostic value and implications for social and neurocognitive deficits in this disorder.

Do adolescents consider mind-body skills groups an acceptable treatment for depression: results from a pilot study.

BACKGROUND: Mind-Body Skills Groups (MBSGs) have shown promise in reducing adolescent depression symptoms; however, little is known about adolescents' perspectives on this treatment. The objective of this study was to understand the acceptability of a new treatment for depressed adolescents in primary care settings. METHODS: Adolescents participating in a 10-week MBSG treatment were interviewed to understand their perspectives on the acceptability and effectiveness of the treatment. Interviews were collected at post-intervention and at a 3-month follow-up visit. RESULTS: A total of 39 adolescents completed both the post-intervention and 3-month follow-up interview. At post-intervention and follow-up, 84% of adolescents stated the MBSGs helped them. When asked how the MBSGs helped them, 3 areas were identified: learning new MBSG activities and skills, social connection with others within the group, and outcomes related to the group. Many adolescents reported no concerns with the MBSGs (49% at post- intervention; 62% at follow-up). Those with concerns identified certain activities as not being useful, wanting the group to be longer, and the time of group (after school) being inconvenient. Most adolescents reported that their life had changed because of the group (72% at post-intervention; 61% at follow-up), and when asked how, common responses included feeling less isolated and more hopeful. CONCLUSIONS: Adolescents found the MBSGs to be helpful and acceptable as a treatment option for depression in primary care. Given the strong emphasis on treatment preference autonomy and the social activities within the group, MBSGs appear well-suited for this age group. TRIAL REGISTRATION: NCT03363750 ; December 6th, 2017.

Clinging on to alpine life: Investigating factors driving the uphill range contraction and population decline of a mountain breeding bird.

Climate change and anthropogenic nitrogen deposition are widely regarded as important drivers of environmental change in alpine habitats. However, due to the difficulties working in high-elevation mountain systems, the impacts of these drivers on alpine breeding species have rarely been investigated. The Eurasian dotterel (Charadrius morinellus) is a migratory wader, which has been the subject of uniquely long-term and spatially widespread monitoring effort in Scotland, where it breeds in alpine areas in dwindling numbers. Here we analyse data sets spanning three decades, to investigate whether key potential drivers of environmental change in Scottish mountains (snow lie, elevated summer temperatures and nitrogen deposition) have contributed to the population decline of dotterel. We also consider the role of rainfall on the species' wintering grounds in North Africa. We found that dotterel declines-in both density and site occupancy of breeding males-primarily occurred on low and intermediate elevation sites. High-elevation sites mostly continued to be occupied, but males occurred at lower densities in years following snow-rich winters, suggesting that high-elevation snow cover displaced dotterel to lower sites. Wintering ground rainfall was positively associated with densities of breeding males two springs later. Dotterel densities were reduced at low and intermediate sites where nitrogen deposition was greatest, but not at high-elevation sites. While climatic factors explained variation in breeding density between years, they did not seem to explain the species' uphill retreat and decline. We cannot rule out the possibility that dotterel have increasingly settled on higher sites previously unavailable due to extensive snow cover, while changes associated with nitrogen deposition may also have rendered lower lying sites less suitable for breeding. Causes of population and range changes in mountain-breeding species are thus liable to be complex, involving multiple anthropogenic drivers of environmental change acting widely across annual and migratory life cycles.

Mediators of focused psychosocial support interventions for children in low-resource humanitarian settings: analysis from an Individual Participant Dataset with 3,143 participants.

BACKGROUND: Research on psychosocial interventions has been focused on the effectiveness of psychosocial interventions on mental health outcomes, without exploring how interventions achieve beneficial effects. Identifying the potential pathways through which interventions work would potentially allow further strengthening of interventions by emphasizing specific components connected with such pathways. METHODS: We conducted a preplanned mediation analysis using individual participant data from a dataset of 11 randomized controlled trials (RCTs) which compared focused psychosocial support interventions versus control conditions for children living in low- and middle-income countries (LMICs) affected by humanitarian crises. Based on an ecological resilience framework, we hypothesized that (a) coping, (b) hope, (c) social support, and (d) functional impairment mediate the relationship between intervention and outcome PTSD symptoms. A systematic search on the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed, PyscARTICLES, Web of Science, and the main local LMICs databases was conducted up to August 2018. The hypotheses were tested by using individual participant data obtained from study authors of all the studies included in the systematic review. RESULTS: We included 3,143 children from 11 studies (100% of data from included studies), of which 1,877 from six studies contributed to the mediation analysis. Functional impairment was the strongest mediator for focused psychosocial interventions on PTSD (mediation coefficient -0.087, standard error 0.040). The estimated proportion of effect mediated by functional impairment, and adjusted for confounders, was 31%. CONCLUSIONS: Findings did not support the proposed mediation hypotheses for coping, hope, and social support. The mediation through functional impairment may represent unmeasured proxy measures or point to a broader mechanism that impacts self-efficacy and agency.

Structure of the Sac3 RNA-binding M-region in the Saccharomyces cerevisiae TREX-2 complex.

Transcription-export complex 2 (TREX-2, or THSC) facilitates localization of actively transcribing genes such as GAL1 to the nuclear periphery, contributes to the generation of export-competent mRNPs and influences gene expression through interactions with Mediator. TREX-2 is based on a Sac3 scaffold to which Thp1, Sem1, Cdc31 and Sus1 bind and consists of three modules: the N-region (Sac3∼1-100), which binds mRNA export factor Mex67:Mtr2; the M-region, in which Thp1 and Sem1 bind to Sac3∼100-550; and the CID region in which Cdc31 and two Sus1 chains bind to Sac3∼720-805. Although the M-region of Sac3 was originally thought to encompass residues ∼250-550, we report here the 2.3Å resolution crystal structure of a complex containing Sac3 residues 60-550 that indicates that the TPR-like repeats of the M-region extend to residue 137 and that residues 90-125 form a novel loop that links Sac3 to Thp1. These new structural elements are important for growth and mRNA export in vivo. Although deleting Sac3 residues 1-90 produced a wild-type phenotype, deletion of the loop as well generated growth defects at 37°C, whereas the deletion of residues 1-250 impaired mRNA export and also generated longer lag times when glucose or raffinose was replaced by galactose as the carbon source.

Structural basis for the dimerization of Nab2 generated by RNA binding provides insight into its contribution to both poly(A) tail length determination and transcript compaction in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae generation of export-competent mRNPs terminates the nuclear phase of the gene expression pathway and facilitates transport to the cytoplasm for translation. Nab2 functions in this process to control both mRNP compaction that facilitates movement through nuclear pore complexes and the length of transcript poly(A) tails. Nab2 has a modular structure that includes seven CCCH Zn fingers that bind to A-rich RNAs and fingers 5­7 are critical for these functions. Here, we demonstrate, using both biophysical and structural methods, that binding A11G RNA induces dimerization of Zn fingers 5­7 mediated by the novel spatial arrangement of the fingers promoting each RNA chain binding two protein chains. The dimerization of Nab2 induced by RNA binding provides a basis for understanding its function in both poly(A) tail length regulation and in the compaction of mature transcripts to facilitate nuclear export.

SMARTA: Automated testing apparatus for visual discrimination tasks.

This article introduces the open-source Subject-Mediated Automatic Remote Testing Apparatus (SMARTA) for visual discrimination tasks, which aims to streamline and ease data collection, eliminate or reduce observer error, increase interobserver agreement, and automate data entry without the need for an internet connection. SMARTA is inexpensive and easy to build, and it can be modified to accommodate a variety of experimental designs. Here we describe the utility and functionality of SMARTA in a captive setting. We present the results from a case study of color vision in ruffed lemurs (Varecia spp.) at the Duke Lemur Center in Durham, North Carolina, in which we demonstrate SMARTA's utility for two-choice color discrimination tasks, as well as its ability to streamline and standardize data collection. We also include detailed instructions for constructing and implementing the fully integrated SMARTA touchscreen system.

Quantification and statistical analysis of the transient visual evoked potential to a contrast-reversing pattern: A frequency-domain approach.

Visual function is often assessed by recording transient visual evoked potentials to contrast reversal of spatial patterns (tVEP-CR). This technique relies on measurements of amplitudes and peak times of a few points in the time-domain waveform, which require subjective selection of appropriate time points in a possibly noisy waveform and ignores much of the informational content in the response. Here, we introduce a set of frequency-domain measures that capture the full content of the response. Magnitude-squared coherence is used to determine the significance and reliability of magnitude measures; estimates of time delay are based on frequency-domain phase measures. In Study 1, extensive testing of a small number of observers revealed response details, and in Study 2, testing of a larger sample verified the novel frequency-domain measures and demonstrated the validity of a short-duration technique to produce reliable tVEP-CRs. In addition, Study 2 revealed adaptation effects present under prolonged stimulation conditions. Principal component analyses provided evidence for six distinct frequency mechanisms, and comparisons with time-domain measures indicated that power in high-frequency bands may be used as objective measures of excitatory input to visual cortex. A middle-frequency band captures the major peaks in the tVEP-CR waveform, and its power is highly correlated with the standard peak-to-trough amplitude measure. These novel frequency-domain indices may serve as more precise and powerful tools to assess visual function in healthy and diseased states.

Cortical brightness adaptation when darkness and brightness produce different dynamical states in the visual cortex.

Darkness and brightness are very different perceptually. To understand the neural basis for the visual difference, we studied the dynamical states of populations of neurons in macaque primary visual cortex when a spatially uniform area (8° × 8°) of the visual field alternated between black and white. Darkness evoked sustained nerve-impulse spiking in primary visual cortex neurons, but bright stimuli evoked only a transient response. A peak in the local field potential (LFP) γ band (30-80 Hz) occurred during darkness; white-induced LFP fluctuations were of lower amplitude, peaking at 25 Hz. However, the sustained response to white in the evoked LFP was larger than for black. Together with the results on spiking, the LFP results imply that, throughout the stimulus period, bright fields evoked strong net sustained inhibition. Such cortical brightness adaptation can explain many perceptual phenomena: interocular speeding up of dark adaptation, tonic interocular suppression, and interocular masking.

Nonlinear dynamics of cortical responses to color in the human cVEP.

The main finding of this paper is that the human visual cortex responds in a very nonlinear manner to the color contrast of pure color patterns. We examined human cortical responses to color checkerboard patterns at many color contrasts, measuring the chromatic visual evoked potential (cVEP) with a dense electrode array. Cortical topography of the cVEPs showed that they were localized near the posterior electrode at position Oz, indicating that the primary cortex (V1) was the major source of responses. The choice of fine spatial patterns as stimuli caused the cVEP response to be driven by double-opponent neurons in V1. The cVEP waveform revealed nonlinear color signal processing in the V1 cortex. The cVEP time-to-peak decreased and the waveform's shape was markedly narrower with increasing cone contrast. Comparison of the linear dynamics of retinal and lateral geniculate nucleus responses with the nonlinear dynamics of the cortical cVEP indicated that the nonlinear dynamics originated in the V1 cortex. The nature of the nonlinearity is a kind of automatic gain control that adjusts cortical dynamics to be faster when color contrast is greater.

Brightness-color interactions in human early visual cortex.

The interaction between brightness and color causes there to be different color appearance when one and the same object is viewed against surroundings of different brightness. Brightness contrast causes color to be desaturated, as has been found in perceptual experiments on color induction and color-gamut expansion in human vision. However, it is not clear yet where in the cerebral cortex the brightness-color interaction that causes these major perceptual effects is located. One hypothesis is that brightness and color signals are processed separately and in parallel within the primary visual cortex V1 and only interact in extrastriate cortex. Another hypothesis is that color and brightness contrast interact strongly already within V1. We localized the brightness-color interaction in human V1 by means of recording the chromatic visual-evoked potential. The chromatic visual-evoked potential measurements decisively support the idea that brightness-color interaction arises in a recurrent inhibitory network in V1. Furthermore, our results show that the inhibitory signal for brightness-color interaction is generated by local brightness contrast at the boundary between target and surround, instead of by the luminance difference between the interior of the color target and its large background.

The duration of reaching movement is longer than predicted by minimum variance.

Whether the central nervous system minimizes variability or effort in planning arm movements can be tested by measuring the preferred movement duration and end-point variability. Here we conducted an experiment in which subjects performed arm reaching movements without visual feedback in fast-, medium-, slow-, and preferred-duration conditions. Results show that 1) total end-point variance was smallest in the medium-duration condition and 2) subjects preferred to carry out movements that were slower than this medium-duration condition. A parsimonious explanation for the overall pattern of end-point errors across fast, medium, preferred, and slow movement durations is that movements are planned to minimize effort as well as end-point error due to both signal-dependent and constant noise.

Host cytoskeleton in respiratory syncytial virus assembly and budding.

Respiratory syncytial virus (RSV) is one of the major pathogens responsible for lower respiratory tract infections (LRTI) in young children, the elderly, and the immunosuppressed. Currently, there are no antiviral drugs or vaccines available that effectively target RSV infections, proving a significant challenge in regards to prevention and treatment. An in-depth understanding of the host-virus interactions that underlie assembly and budding would inform new targets for antiviral development.Current research suggests that the polymerised form of actin, the filamentous or F-actin, plays a role in RSV assembly and budding. Treatment with cytochalasin D, which disrupts F-actin, has been shown to inhibit virus release. In addition, the actin cytoskeleton has been shown to interact with the RSV matrix (M) protein, which plays a central role in RSV assembly. For this reason, the interaction between these two components is hypothesised to facilitate the movement of viral components in the cytoplasm and to the budding site. Despite increases in our knowledge of RSV assembly and budding, M-actin interactions are not well understood. In this review, we discuss the current literature on the role of actin cytoskeleton during assembly and budding of RSV with the aim to integrate disparate studies to build a hypothetical model of the various molecular interactions between actin and RSV M protein that facilitate RSV assembly and budding.

RNA recognition and self-association of CPEB4 is mediated by its tandem RRM domains.

Cytoplasmic polyadenylation is regulated by the interaction of the cytoplasmic polyadenylation element binding proteins (CPEB) with cytoplasmic polyadenylation element (CPE) containing mRNAs. The CPEB family comprises four paralogs, CPEB1-4, each composed of a variable N-terminal region, two RNA recognition motif (RRM) and a C-terminal ZZ-domain. We have characterized the RRM domains of CPEB4 and their binding properties using a combination of biochemical, biophysical and NMR techniques. Isothermal titration calorimetry, NMR and electrophoretic mobility shift assay experiments demonstrate that both the RRM domains are required for an optimal CPE interaction and the presence of either one or two adenosines in the two most commonly used consensus CPE motifs has little effect on the affinity of the interaction. Both the single RRM1 and the tandem RRM1-RRM2 have the ability to dimerize, although representing a minor population. Self-association does not affect the proteins' ability to interact with RNA as demonstrated by ion mobility-mass spectrometry. Chemical shift effects measured by NMR of the apo forms of the RRM1-RRM2 samples indicate that the two domains are orientated toward each other. NMR titration experiments show that residues on the ß-sheet surface on RRM1 and at the C-terminus of RRM2 are affected upon RNA binding. We propose a model of the CPEB4 RRM1-RRM2-CPE complex that illustrates the experimental data.

Identification of novel non-canonical RNA-binding sites in Gemin5 involved in internal initiation of translation.

Ribonucleic acid (RNA)-binding proteins are key players of gene expression control. We have shown that Gemin5 interacts with internal ribosome entry site (IRES) elements and modulates initiation of translation. However, little is known about the RNA-binding sites of this protein. Here we show that the C-terminal region of Gemin5 bears two non-canonical bipartite RNA-binding sites, encompassing amino acids 1297-1412 (RBS1) and 1383-1508 (RBS2). While RBS1 exhibits greater affinity for RNA than RBS2, it does not affect IRES-dependent translation in G5-depleted cells. In solution, the RBS1 three-dimensional structure behaves as an ensemble of flexible conformations rather than having a defined tertiary structure. However, expression of the polypeptide G51383-1508, bearing the low RNA-binding affinity RBS2, repressed IRES-dependent translation. A comparison of the RNA-binding capacity and translation control properties of constructs expressed in mammalian cells to that of the Gemin5 proteolysis products observed in infected cells reveals that non-repressive products accumulated during infection while the repressor polypeptide is not stable. Taken together, our results define the low affinity RNA-binding site as the minimal element of the protein being able to repress internal initiation of translation.

Development and evaluation of a clinical model for lung cancer patients using stereotactic body radiotherapy (SBRT) within a knowledge-based algorithm for treatment planning.

The purpose of this study was to describe the development of a clinical model for lung cancer patients treated with stereotactic body radiotherapy (SBRT) within a knowledge-based algorithm for treatment planning, and to evaluate the model performance and applicability to different planning techniques, tumor locations, and beam arrangements. 105 SBRT plans for lung cancer patients previously treated at our institution were included in the development of the knowledge-based model (KBM). The KBM was trained with a combination of IMRT, VMAT, and 3D CRT techniques. Model performance was validated with 25 cases, for both IMRT and VMAT. The full KBM encompassed lesions located centrally vs. peripherally (43:62), upper vs. lower (62:43), and anterior vs. posterior (60:45). Four separate sub-KBMs were created based on tumor location. Results were compared with the full KBM to evaluate its robustness. Beam templates were used in conjunction with the optimizer to evaluate the model's ability to handle suboptimal beam placements. Dose differences to organs-at-risk (OAR) were evaluated between the plans gener-ated by each KBM. Knowledge-based plans (KBPs) were comparable to clinical plans with respect to target conformity and OAR doses. The KBPs resulted in a lower maximum spinal cord dose by 1.0 ± 1.6 Gy compared to clinical plans, p = 0.007. Sub-KBMs split according to tumor location did not produce significantly better DVH estimates compared to the full KBM. For central lesions, compared to the full KBM, the peripheral sub-KBM resulted in lower dose to 0.035 cc and 5 cc of the esophagus, both by 0.4Gy ± 0.8Gy, p = 0.025. For all lesions, compared to the full KBM, the posterior sub-KBM resulted in higher dose to 0.035 cc, 0.35 cc, and 1.2 cc of the spinal cord by 0.2 ± 0.4Gy, p = 0.01. Plans using template beam arrangements met target and OAR criteria, with an increase noted in maximum heart dose (1.2 ± 2.2Gy, p = 0.01) and GI (0.2 ± 0.4, p = 0.01) for the nine-field plans relative to KBPs planned with custom beam angles. A knowledge-based model for lung SBRT consisting of multiple treatment modalities and lesion loca-tions produced comparable plan quality to clinical plans. With proper training and validation, a robust KBM can be created that encompasses both IMRT and VMAT techniques, as well as different lesion locations.

Characterization and evaluation of 2.5 MV electronic portal imaging for accurate localization of intra- and extracranial stereotactic radiosurgery.

2.5 MV electronic portal imaging, available on Varian TrueBeam machines, was characterized using various phantoms in this study. Its low-contrast detectability, spatial resolution, and contrast-to-noise ratio (CNR) were compared with those of conventional 6 MV and kV planar imaging. Scatter effect in large patient body was simulated by adding solid water slabs along the beam path. The 2.5 MV imaging mode was also evaluated using clinically acquired images from 24 patients for the sites of brain, head and neck, lung, and abdomen. With respect to 6 MV, the 2.5 MV achieved higher contrast and preserved sharpness on bony structures with only half of the imaging dose. The quality of 2.5 MV imaging was comparable to that of kV imaging when the lateral separation of patient was greater than 38 cm, while the kV image quality degraded rapidly as patient separation increased. Based on the results of patient images, 2.5 MV imaging was better for cranial and extracranial SRS than the 6 MV imaging.