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25 High-resolution MRI Reveals Selective Patterns of Hippocampal Subfield Atrophy in Focal Epilepsy
- Adam Schadler, Erik Kaestner, Alena Stasenko, Christine N. Smith, Catherine Tallman, Nigel P. Pedersen, Shahin Hakimian, Michelle S. Kim, Daniel J Peterson, Thomas J. Grabowski, Daniel L. Drane, Carrie R. McDonald
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 25-26
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Objective:
Hippocampal pathology is a consistent feature in persons with temporal lobe epilepsy (TLE) and a strong biomarker of memory impairment. Histopathological studies have identified selective patterns of cell loss across hippocampal subfields in TLE, the most common being cellular loss in the cornu ammonis 1 (CA1) and dentage gyrus (DG). Structural neuroimaging provides a non-invasive method to understand hippocampal pathology, but traditionally only at a whole-hippocampal level. However, recent methodological advances have enabled the non-invasive quantification of subfield pathology in patients, enabling potential integration into clinical workflow. In this study, we characterize patterns of hippocampal subfield atrophy in patients with TLE and examine the associations between subfield atrophy and clinical characteristics.
Participants and Methods:High-resolution T2 and T1-weighted MRI were collected from 31 participants (14 left TLE; 6 right TLE; 11 healthy controls [HC], aged 18-61 years). Reconstructions of hippocampal subfields and estimates of their volumes were derived using the Automated Segmentation of Hippocampal Subfields (ASHS) pipeline. Total hippocampal volume was calculated by combining estimates of the subfields CA1-3, DG, and subiculum. To control for variations in head size, all volume estimates were divided by estimates of total brain volume. To assess disease effects on hippocampal atrophy, hippocampi were recoded as either ipsilateral or contralateral to the side of seizure focus. Two sample t-tests at a whole-hippocampus level were used to test for ipsilateral and contralateral volume loss in patients relative to HC. To assess whether we replicated the selective histopathological patterns of subfield atrophy, we carried out mixed-effects ANOVA, coding for an interaction between diagnostic group and hippocampal subfield. Finally, to assess effects of disease load, non-parametric correlations were performed between subfield volume and age of first seizure and duration of illness.
Results:Patients had significantly smaller total ipsilateral hippocampal volume compared with HC (d=1.23, p<.005). Contralateral hippocampus did not significantly differ between TLE and HC. Examining individual subfields for the ipsilateral hemisphere revealed significant main-effects for group (F(1, 29)=8.2, p<0.01), subfields (F(4, 115)=550.5, p<0.005), and their interaction (F(4, 115)=8.1, p<0.001). Post-hoc tests revealed that TLE had significantly smaller volume in the ipsilateral CA1 (d=-2.0, p<0.001) and DG (d = -1.4, p<0.005). Longer duration of illness was associated with smaller volume of ipsilateral CA2 (p=-0.492, p<0.05) and larger volume of contralateral whole-hippocampus (p=0.689, p<0.001), CA1 (p=0.614, p < 0.005), and DG (p=0.450, p<0.05).
Conclusions:Histopathological characterization after surgery has revealed important associations between hippocampal subfield cell loss and memory impairments in patients with TLE. Here we demonstrate that non-invasive neuroimaging can detect a pattern of subfield atrophy in TLE (i.e., CA1/DG) that matches the most common form of histopathologically-observed hippocampal sclerosis in TLE (HS Type 1) and has been linked directly to both verbal and visuospatial memory impairment. Finally, we found evidence that longer disease duration is associated with larger contralateral hippocampal volume, driven by increases in CA1 and DG. This may reflect subfield-specific functional reorganization to the unaffected brain tissue, a compensatory effect which may have important implications for patient function and successful treatment outcomes.
Monte Carlo evaluation of target dose coverage in lung stereotactic body radiation therapy with flattening filter-free beams
- Oleg N. Vassiliev, Christine B. Peterson, Joe Y. Chang, Radhe Mohan
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- Journal:
- Journal of Radiotherapy in Practice / Volume 21 / Issue 1 / March 2022
- Published online by Cambridge University Press:
- 16 October 2020, pp. 81-87
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Aim:
Previous studies showed that replacing conventional flattened beams (FF) with flattening filter-free (FFF) beams improves the therapeutic ratio in lung stereotactic body radiation therapy (SBRT), but these findings could have been impacted by dose calculation uncertainties caused by the heterogeneity of the thoracic anatomy and by respiratory motion, which were particularly high for target coverage. In this study, we minimised such uncertainties by calculating doses using high-spatial-resolution Monte Carlo and four-dimensional computed tomography (4DCT) images. We aimed to evaluate more reliably the benefits of using FFF beams for lung SBRT.
Materials and methods:For a cohort of 15 patients with early-stage lung cancer that we investigated in a previous treatment planning study, we recalculated dose distributions with Monte Carlo using 4DCT images. This included 15 FF and 15 FFF treatment plans.
Results:Compared to Monte Carlo, the treatment planning system (TPS) over-predicted doses in low-dose regions of the planning target volume (PTV). For most patients, replacing FF beams with FFF beams improved target coverage, tumour control, and uncomplicated tumour control probabilities.
Conclusions:Monte Carlo tends to reveal deficiencies in target coverage compared to coverage predicted by the TPS. Our data support previously reported benefits of using FFF beams for lung SBRT.
Using FFF beams to improve the therapeutic ratio of lung SBRT
- Oleg N. Vassiliev, Christine B. Peterson, Joe Y. Chang, Radhe Mohan
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- Journal:
- Journal of Radiotherapy in Practice / Volume 20 / Issue 4 / December 2021
- Published online by Cambridge University Press:
- 30 July 2020, pp. 419-425
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Aim:
The aim of this study was to investigate the extent to which lung stereotactic body radiotherapy (SBRT) treatment plans can be improved by replacing conventional flattening filter (FF) beams with flattening filter-free (FFF) beams.
Materials and methods:We selected 15 patients who had received SBRT with conventional 6-MV photon beams for early-stage lung cancer. We imported the patients’ treatment plans into the Eclipse 13·6 treatment planning system, in which we configured the AAA dose calculation model using representative beam data for a TrueBeam accelerator operated in 6-MV FFF mode. We then created new treatment plans by replacing the conventional FF beams in the original plans with FFF beams.
Results:The FFF plans had better target coverage than the original FF plans did. For the planning target volume, FFF plans significantly improved the D98, D95, D90, homogeneity index and uncomplicated tumour control probability. In most cases, the doses to organs at risk were lower in FFF plans. FFF plans significantly reduced the mean lung dose, V10, V20, V30, and normal tissue complication probability for the total lung and improved the dosimetric indices for the ipsilateral lung. For most patients, FFF beams achieved lower maximum doses to the oesophagus, heart and the spinal cord, and a lower chest wall V30.
Conclusions:Compared with FF beams, FFF beams achieved lower doses to organs at risk, especially the lung, without compromising tumour coverage; in fact, FFF beams improved coverage in most cases. Thus, replacing FF beams with FFF beams can achieve a better therapeutic ratio.
Efficacy of digital CBT for insomnia to reduce depression across demographic groups: a randomized trial
- Philip Cheng, Annemarie I. Luik, Cynthia Fellman-Couture, Edward Peterson, Christine L.M. Joseph, Gabriel Tallent, Kieulinh Michelle Tran, Brian K. Ahmedani, Timothy Roehrs, Thomas Roth, Christopher L. Drake
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- Journal:
- Psychological Medicine / Volume 49 / Issue 3 / February 2019
- Published online by Cambridge University Press:
- 24 May 2018, pp. 491-500
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Background
Insomnia and depression are highly comorbid and mutually exacerbate clinical trajectories and outcomes. Cognitive behavioral therapy for insomnia (CBT-I) effectively reduces both insomnia and depression severity, and can be delivered digitally. This could substantially increase the accessibility to CBT-I, which could reduce the health disparities related to insomnia; however, the efficacy of digital CBT-I (dCBT-I) across a range of demographic groups has not yet been adequately examined. This randomized placebo-controlled trial examined the efficacy of dCBT-I in reducing both insomnia and depression across a wide range of demographic groups.
MethodsOf 1358 individuals with insomnia randomized, a final sample of 358 were retained in the dCBT-I condition and 300 in the online sleep education condition. Severity of insomnia and depression was examined as a dependent variable. Race, socioeconomic status (SES; household income and education), gender, and age were also tested as independent moderators of treatment effects.
ResultsThe dCBT-I condition yielded greater reductions in both insomnia and depression severity than sleep education, with significantly higher rates of remission following treatment. Demographic variables (i.e. income, race, sex, age, education) were not significant moderators of the treatment effects, suggesting that dCBT-I is comparably efficacious across a wide range of demographic groups. Furthermore, while differences in attrition were found based on SES, attrition did not differ between white and black participants.
ConclusionsResults provide evidence that the wide dissemination of dCBT-I may effectively target both insomnia and comorbid depression across a wide spectrum of the population.
Contributors
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- By Tod C. Aeby, Melanie D. Altizer, Ronan A. Bakker, Meghann E. Batten, Anita K. Blanchard, Brian Bond, Megan A. Brady, Saweda A. Bright, Ellen L. Brock, Amy Brown, Ashley Carroll, Jori S. Carter, Frances Casey, Weldon Chafe, David Chelmow, Jessica M. Ciaburri, Stephen A. Cohen, Adrianne M. Colton, PonJola Coney, Jennifer A. Cross, Julie Zemaitis DeCesare, Layson L. Denney, Megan L. Evans, Nicole S. Fanning, Tanaz R. Ferzandi, Katie P. Friday, Nancy D. Gaba, Rajiv B. Gala, Andrew Galffy, Adrienne L. Gentry, Edward J. Gill, Philippe Girerd, Meredith Gray, Amy Hempel, Audra Jolyn Hill, Chris J. Hong, Kathryn A. Houston, Patricia S. Huguelet, Warner K. Huh, Jordan Hylton, Christine R. Isaacs, Alison F. Jacoby, Isaiah M. Johnson, Nicole W. Karjane, Emily E. Landers, Susan M. Lanni, Eduardo Lara-Torre, Lee A. Learman, Nikola Alexander Letham, Rachel K. Love, Richard Scott Lucidi, Elisabeth McGaw, Kimberly Woods McMorrow, Christopher A. Manipula, Kirk J. Matthews, Michelle Meglin, Megan Metcalf, Sarah H. Milton, Gaby Moawad, Christopher Morosky, Lindsay H. Morrell, Elizabeth L. Munter, Erin L. Murata, Amanda B. Murchison, Nguyet A. Nguyen, Nan G. O’Connell, Tony Ogburn, K. Nathan Parthasarathy, Thomas C. Peng, Ashley Peterson, Sarah Peterson, John G. Pierce, Amber Price, Heidi J. Purcell, Ronald M. Ramus, Nicole Calloway Rankins, Fidelma B. Rigby, Amanda H. Ritter, Barbara L. Robinson, Danielle Roncari, Lisa Rubinsak, Jennifer Salcedo, Mary T. Sale, Peter F. Schnatz, John W. Seeds, Kathryn Shaia, Karen Shelton, Megan M. Shine, Haller J. Smith, Roger P. Smith, Nancy A. Sokkary, Reni A. Soon, Aparna Sridhar, Lilja Stefansson, Laurie S. Swaim, Chemen M. Tate, Hong-Thao Thieu, Meredith S. Thomas, L. Chesney Thompson, Tiffany Tonismae, Angela M. Tran, Breanna Walker, Alan G. Waxman, C. Nathan Webb, Valerie L. Williams, Sarah B. Wilson, Elizabeth M. Yoselevsky, Amy E. Young
- Edited by David Chelmow, Virginia Commonwealth University, Christine R. Isaacs, Virginia Commonwealth University, Ashley Carroll, Virginia Commonwealth University
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- Book:
- Acute Care and Emergency Gynecology
- Published online:
- 05 November 2014
- Print publication:
- 30 October 2014, pp ix-xiv
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10 - Bayesian Model Averaging for Genetic Association Studies
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- By Christine Peterson, Rice University, Michael Swartz, The University of Texas, Sanjay Shete, The University of Texas, Marina Vannucci, Rice University
- Edited by Kim-Anh Do, Zhaohui Steve Qin, Emory University, Atlanta, Marina Vannucci, Rice University, Houston
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- Book:
- Advances in Statistical Bioinformatics
- Published online:
- 05 June 2013
- Print publication:
- 10 June 2013, pp 208-223
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Summary
Genetic Association Studies
Genetic association studies seek to identify genetic variants associated with a particular disease or phenotype. Typically, the phenotype of interest will be a complex trait that is not determined by a single recessive, additive, or dominant allele (Lander and Schork, 1994). Although there has been a shift in recent years toward genome-wide association studies(GWAS) that agnostically test all single-nucleotide polymorphisms (SNPs) for association with a disease, many genetic association studies still focus on candidate genes that have functions known to be related to the phenotype. Although it is scientifically preferable to include as many SNPs as possible, the number of SNPs in a study is often limited by practical constraints such as cost. The statistical methods discussed in this chapter are primarily applicable to studies using several hundred SNPs. For a discussion of Bayesian approaches for full-scale GWAS, which may include up to 1 million SNPs, see Chapters 9 and 11.
A variety of study designs for genetic association studies have been proposed; for a comparison, see Cordell and Clayton (2005). The most common design for binary outcomes is the population-based case-control study. Family-based designs, which examine patterns of inheritance in related individuals, are also useful, particularly when the variant of interest is rare in the overall population. Data for family studies may come from extended pedigrees or from triads of affected offspring and their parents. In the case-parent triad design, disease-associated SNPs are identified using the transmission disequilibrium test (TDT), which is based on the idea that affected children will have nonrandom inheritance of causal genetic variants from their parents.
Notes on contributors
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- By Christine Alexander, Simon Avery, Michael Baumber, Birgitta Berglund, Dinah Birch, Miriam Elizabeth Burstein, Janis McLarren Caldwell, Edward Chitham, Stephen Colclough, Ann Dinsdale, Bob Duckett, Maria Frawley, Barbara T. Gates, Janet Gezari, Dudley Green, David Jasper, Drew Lamonica Arms, Elizabeth Langland, Alexandra Lewis, Sara J. Lodge, Sue Lonoff, Jill L. Matus, Victor A. Neufeldt, Linda H. Peterson, Stephen Prickett, Lyn Pykett, Herbert Rosengarten, Jane Sellars, Joanne Shattock, Margaret Smith, Patsy Stoneman, Marianne Thormählen, Ian Ward, Stephen Whitehead, T. J. Winnifrith, Steven Wood
- Edited by Marianne Thormählen, Lunds Universitet, Sweden
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- Book:
- The Brontës in Context
- Published online:
- 05 December 2012
- Print publication:
- 01 November 2012, pp xi-xvii
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Multilayer Materials for Electrostatic Switches
- Mark A Phillips, Brennan L Peterson, Christine M Esber, Jesse Hwang, Bruce M Clemens
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- Journal:
- MRS Online Proceedings Library Archive / Volume 657 / 2000
- Published online by Cambridge University Press:
- 17 March 2011, EE5.1
- Print publication:
- 2000
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Metal multilayers are a unique way to manufacture reliable conductive members for MEMS devices. These members are particularly suited for electrostatic switches. Unlike elemental Al, which experiences curvature problems during processing, the residual stress in these beams can be controlled and calibrated during stress measurements to have repeatable shapes and stresses upon release. In this study, curvature experiments were performed to determine the optimal deposition parameters (pressure, thickness) to produce metal multilayer beams with zero average stress and zero bending moment, which can be obtained by alternating tensile and compressive layers within. Resistivity measurements were made to determine the effect of interfaces on resistivity.