Impact of upfront adjuvant chemoradiation on survival in patients with molecularly defined oligodendroglioma: the benefits of PCV over TMZ.

PURPOSE: Oligodendroglioma is an adult-type diffuse glioma defined by 1p/19q codeletion and IDH1/2 mutation. Treatment includes surgery followed by observation alone in select low-grade tumors, or combination radiation and chemotherapy with procarbazine, lomustine, and vincristine (PCV) or temozolomide (TMZ). While prospective studies investigating treatments for molecularly defined oligodendrogliomas are ongoing, this retrospective study analyzes the relationship between adjuvant regimens and progression-free survival (PFS). METHODS: Adults with IDH-mutant, 1p/19q codeleted oligodendroglioma (WHO grade 2 or 3) who underwent surgery between 2005 and 2021 were identified. Clinical data, disease characteristics, treatment, and outcomes were collected. RESULTS: A total of 207 patients with grade 2 and 70 with grade 3 oligodendrogliomas were identified. Median (IQR) follow-up was 57 (87) months. Patients with grade 3 tumors who received adjuvant radiation and PCV had longer median PFS (> 110 months) than patients who received radiation and TMZ (52 months, p = 0.008) or no adjuvant chemoradiation (83 months, p = 0.03), which was not seen in grade 2 tumors (p = 0.8). In multivariate analysis, patients who received PCV chemotherapy (Relative Risk [95% CI] = 0.24[0.05-1.08] and radiotherapy (0.46[0.21-1.02]) trended towards longer PFS, independently of grade. CONCLUSION: Adjuvant radiation and PCV are associated with improved PFS over radiation with TMZ in patients with grade 3 molecularly defined oligodendrogliomas, and all-grade patients treated with PCV trended towards decreased risk of recurrence and progression. These results highlight the importance of ongoing clinical trials investigating these treatments.

Clinical Use of Bedside Portable Ultra-Low-Field Brain Magnetic Resonance Imaging in Patients on Extracorporeal Membrane Oxygenation: Results From the Multicenter SAFE MRI ECMO Study.

BACKGROUND: Early detection of acute brain injury (ABI) at the bedside is critical in improving survival for patients with extracorporeal membrane oxygenation (ECMO) support. We aimed to examine the safety of ultra-low-field (ULF; 0.064-T) portable magnetic resonance imaging (pMRI) in patients undergoing ECMO and to investigate the ABI frequency and types with ULF-pMRI. METHODS: This was a multicenter prospective observational study (SAFE MRI ECMO study [Assessing the Safety and Feasibility of Bedside Portable Low-Field Brain Magnetic Resonance Imaging in Patients on ECMO]; NCT05469139) from 2 tertiary centers (Johns Hopkins, Baltimore, MD and University of Texas-Houston) with specially trained intensive care units. Primary outcomes were safety of ULF-pMRI during ECMO support, defined as completion of ULF-pMRI without significant adverse events. RESULTS: Of 53 eligible patients, 3 were not scanned because of a large head size that did not fit within the head coil. ULF-pMRI was performed in 50 patients (median age, 58 years; 52% male), with 34 patients (68%) on venoarterial ECMO and 16 patients (32%) on venovenous ECMO. Of 34 patients on venoarterial ECMO, 11 (22%) were centrally cannulated and 23 (46%) were peripherally cannulated. In venovenous ECMO, 9 (18%) had single-lumen cannulation and 7 (14%) had double-lumen cannulation. Of 50 patients, adverse events occurred in 3 patients (6%), with 2 minor adverse events (ECMO suction event; transient low ECMO flow) and one serious adverse event (intra-aortic balloon pump malfunction attributable to electrocardiographic artifacts). All images demonstrated discernible intracranial pathologies with good quality. ABI was observed in 22 patients (44%). Ischemic stroke (36%) was the most common type of ABI, followed by intracranial hemorrhage (6%) and hypoxic-ischemic brain injury (4%). Of 18 patients (36%) with both ULF-pMRI and head computed tomography within 24 hours, ABI was observed in 9 patients with a total of 10 events (8 ischemic, 2 hemorrhagic events). Of the 8 ischemic events, pMRI observed all 8, and head computed tomography observed only 4 events. For intracranial hemorrhage, pMRI observed only 1 of them, and head computed tomography observed both (2 events). CONCLUSIONS: Our study demonstrates that ULF-pMRI can be performed in patients on ECMO across different ECMO cannulation strategies in specially trained intensive care units. The incidence of ABI was high, seen in 44% of ULF-pMRI studies. ULF-pMRI imaging appears to be more sensitive to ABI, particularly ischemic stroke, compared with head computed tomography.

Diagnostic Performance of ASL-MRI and FDG-PET in Frontotemporal Dementia: A Systematic Review and Meta-Analysis.

BACKGROUND: While the diagnosis of frontotemporal dementia (FTD) is based mostly on clinical features, [18F]-FDG PET has been investigated as a potential imaging golden standard in ambiguous cases, with arterial spin labeling (ASL) MRI gaining recent interest. PURPOSE: The purpose of this study is to conduct a systematic review and meta-analysis on the diagnostic performance of ASL MRI in FTD patients and compare it to that of [18F]-FDG PET. DATA SOURCES: A systematic search of PubMed, Scopus and EMBASE was conducted until March 13, 2024. STUDY SELECTION: Inclusion criteria were: original articles, patients with FTD and/or its variants, use of ASL MR perfusion imaging with or without [18F]-FDG PET, presence of sufficient diagnostic performance data. Exclusion criteria were: meeting abstracts, comments, summaries, protocols, letters and guidelines, longitudinal studies, overlapping cohorts. DATA ANALYSIS: The quality of eligible studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) for [18F]-FDG PET and ASL MRI were calculated, and a summary receiver operating characteristic curve was plotted. DATA SYNTHESIS: Seven eligible studies were identified, which included a total of 102 FTD patients. Aside from some of the studies showing at worst an unclear risk of bias in patient selection, index test, flow and timing, all studies showed low risk of bias and applicability concerns in all categories. Data from 4 studies was included in our meta-analysis for ASL MRI and 3 studies for [18F]-FDG PET. Pooled sensitivity, specificity and DOR were 0.70 (95% CI: 0.59-0.79), 0.81 (95% CI: 0.71-0.88) and 8.00 (95% CI: 3.74-17.13) for ASL MRI, and 0.88 (95% CI: 0.71-0.96), 0.89 (95% CI: 0.43-0.99) and 47.18 (95% CI: 10.77-206.75) for [18F]-FDG PET. LIMITATIONS: The number of studies was relatively small, with a small sample size. The studies used different scanning protocols as well as a mix of diagnostic metrics, all of which might have introduced heterogeneity in the data. CONCLUSIONS: While ASL MRI performed worse than [18F]-FDG PET in the diagnosis of FTD, it exhibited a decent diagnostic performance to justify its further investigation as a quicker and more convenient alternative. ABBREVIATIONS: 3DPCASL, 3D pseudocontinuous ASL; AD, Alzheimer's disease; ASL, arterial spin labeling; AUC, area under the curve; CI, confidence interval; DOR, diagnostic odds ratio; FN, false negative; FP, false positive; FTD, frontotemporal dementia; LE, limbic encephalitis; NLR, negative likelihood ratio; PASL, pulsed ASL; PLD, post-label delay; PLR, positive likelihood ratio; PRISMA, PSP, progressive supranuclear palsy; Preferred Reporting Items for Systematic Reviews and Meta-Analysis; SROC, summary receiver operative characteristic; TN, true negative; TP, true positive; QUADAS-2, Quality Assessment of Diagnostic Accuracy Studies-2.

Asymmetry of the Frontal Aslant Tract Depends on Handedness.

BACKGROUND AND PURPOSE: The human brain displays structural and functional disparities between its hemispheres, with such asymmetry extending to the frontal aslant tract. This plays a role in a variety of cognitive functions, including speech production, language processing, and executive functions. However, the factors influencing the laterality of the frontal aslant tract remain incompletely understood. Handedness is hypothesized to impact frontal aslant tract laterality, given its involvement in both language and motor control. In this study, we aimed to investigate the relationship between handedness and frontal aslant tract lateralization, providing insight into this aspect of brain organization. MATERIALS AND METHODS: The Automated Tractography Pipeline was used to generate the frontal aslant tract for both right and left hemispheres in a cohort of 720 subjects sourced from the publicly available Human Connectome Project in Aging database. Subsequently, macrostructural and microstructural parameters of the right and left frontal aslant tract were extracted for each individual in the study population. The Edinburgh Handedness Inventory scores were used for the classification of handedness, and a comparative analysis across various handedness groups was performed. RESULTS: An age-related decline in both macrostructural parameters and microstructural integrity was noted within the studied population. The frontal aslant tract demonstrated a greater volume and larger diameter in male subjects compared with female participants. Additionally, a left-side laterality of the frontal aslant tract was observed within the general population. In the right-handed group, the volume (P < .001), length (P < .001), and diameter (P = .004) of the left frontal aslant tract were found to be higher than those of the right frontal aslant tract. Conversely, in the left-handed group, the volume (P = .040) and diameter (P = .032) of the left frontal aslant tract were lower than those of the right frontal aslant tract. Furthermore, in the right-handed group, the volume and diameter of the frontal aslant tract showed left-sided lateralization, while in the left-handed group, a right-sided lateralization was evident. CONCLUSIONS: The laterality of the frontal aslant tract appears to differ with handedness. This finding highlights the complex interaction between brain lateralization and handedness, emphasizing the importance of considering handedness as a factor in evaluating brain structure and function.

Genomic Alterations in Molecularly Defined Oligodendrogliomas.

BACKGROUND AND OBJECTIVES: Oligodendrogliomas are defined by IDH1/2 mutation and codeletion of chromosome arms 1p/19q. Although previous studies identified CIC, FUBP1, and TERTp as frequently altered in oligodendrogliomas, the clinical relevance of these molecular signatures is unclear. Moreover, previous studies predominantly used research panels that are not readily available to providers and patients. Accordingly, we explore genomic alterations in molecularly defined oligodendrogliomas using clinically standardized next-generation sequencing (NGS) panels. METHODS: A retrospective single-center study evaluated adults with pathologically confirmed IDH-mutant, 1p/19q-codeleted oligodendrogliomas diagnosed between 2005 and 2021. Genetic data from formalin-fixed, paraffin-embedded specimens were analyzed with the NGS Solid Tumor Panel at the Johns Hopkins Medical Laboratories, which tests more than 400 cancer-related genes. Kaplan-Meier plots and log-rank tests compared progression-free survival (PFS) and overall survival by variant status. χ2 tests, t-tests, and Wilcoxon rank-sum tests were used to compare clinical characteristics between genomic variant status in the 10 most frequently altered genes. RESULTS: Two hundred and seventy-seven patients with molecularly defined oligodendrogliomas were identified, of which 95 patients had available NGS reports. Ten genes had 9 or more patients with a genomic alteration, with CIC, FUBP1, and TERTp being the most frequently altered genes (n = 60, 23, and 22, respectively). Kaplan-Meier curves showed that most genes were not associated with differences in PFS or overall survival. At earlier time points (PFS <100 months), CIC alterations conferred a reduction in PFS in patients (P = .038). CONCLUSION: Our study confirms the elevated frequency of CIC, FUBP1, and TERTp alterations in molecularly defined oligodendrogliomas and suggests a potential relationship of CIC alteration to PFS at earlier time points. Understanding these genomic variants may inform prognosis or therapeutic recommendations as NGS becomes routine.

Prior football or rugby exposure and white matter signal abnormalities in professional male mixed martial arts fighters.

BACKGROUND: White matter signal abnormalities have been associated with traumatic brain injury (TBI) and repetitive head impacts (RHI) in contact sports (e.g. American football, rugby). However, previous studies of mixed martial arts (MMA) fighters from the Professional Fighters Brain Health Study have not found greater white matter signal abnormalities in fighters versus controls. OBJECTIVE: This study aims to explore the varying white matter effects of football/rugby and MMA by analyzing how football/rugby history in mixed martial arts fighters may relate to white matter signal abnormalities, helping to further our understanding of sport-specific brain health risks. METHODS: Baseline visits for 90 active, professional, male mixed martial arts fighters and 27 unexposed male controls were cross-sectionally analyzed. Wilcoxon and Kruskal-Wallis tests compared demographics and white matter signal abnormalities, and multivariable regression models examined the associations between football/rugby history and white matter signal abnormality burden in fighters, adjusting for age, education, race, fights, MRI scanner, and supratentorial volume. RESULTS: 37/90 fighters had football/rugby history (mean: 4 years; range: 1-12 years). White matter signal abnormalities were significantly greater in fighters with football/rugby history compared to fighters without football/rugby history (Wilcoxon, p = 0.0190). Football/rugby history was significantly associated with white matter signal abnormality burden >75th percentile (OR: 12, CI: 3.3-61, p < 0.001) and >50th percentile (OR: 3.2, CI: 1.2-9.4, p = 0.024) in fighters. Years of football/rugby were also significantly associated with white matter signal abnormalities. CONCLUSION: Our findings expand on previous literature by demonstrating a significant relationship between white matter signal abnormalities (WMSAs) and football/rugby history but not MMA. Furthermore, our study suggests an added risk for WMSAs in MMA fighters with a history of football/rugby. Future research should further evaluate WMSAs in contact sports, helping to inform athletes, regulatory bodies, and healthcare providers of the potential brain health risks of contact sports.

Assessing the Performance of Artificial Intelligence Models: Insights from the American Society of Functional Neuroradiology Artificial Intelligence Competition.

BACKGROUND AND PURPOSE: Artificial intelligence models in radiology are frequently developed and validated using data sets from a single institution and are rarely tested on independent, external data sets, raising questions about their generalizability and applicability in clinical practice. The American Society of Functional Neuroradiology (ASFNR) organized a multicenter artificial intelligence competition to evaluate the proficiency of developed models in identifying various pathologies on NCCT, assessing age-based normality and estimating medical urgency. MATERIALS AND METHODS: In total, 1201 anonymized, full-head NCCT clinical scans from 5 institutions were pooled to form the data set. The data set encompassed studies with normal findings as well as those with pathologies, including acute ischemic stroke, intracranial hemorrhage, traumatic brain injury, and mass effect (detection of these, task 1). NCCTs were also assessed to determine if findings were consistent with expected brain changes for the patient's age (task 2: age-based normality assessment) and to identify any abnormalities requiring immediate medical attention (task 3: evaluation of findings for urgent intervention). Five neuroradiologists labeled each NCCT, with consensus interpretations serving as the ground truth. The competition was announced online, inviting academic institutions and companies. Independent central analysis assessed the performance of each model. Accuracy, sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic (ROC) curves were generated for each artificial intelligence model, along with the area under the ROC curve. RESULTS: Four teams processed 1177 studies. The median age of patients was 62 years, with an interquartile range of 33 years. Nineteen teams from various academic institutions registered for the competition. Of these, 4 teams submitted their final results. No commercial entities participated in the competition. For task 1, areas under the ROC curve ranged from 0.49 to 0.59. For task 2, two teams completed the task with area under the ROC curve values of 0.57 and 0.52. For task 3, teams had little-to-no agreement with the ground truth. CONCLUSIONS: To assess the performance of artificial intelligence models in real-world clinical scenarios, we analyzed their performance in the ASFNR Artificial Intelligence Competition. The first ASFNR Competition underscored the gap between expectation and reality; and the models largely fell short in their assessments. As the integration of artificial intelligence tools into clinical workflows increases, neuroradiologists must carefully recognize the capabilities, constraints, and consistency of these technologies. Before institutions adopt these algorithms, thorough validation is essential to ensure acceptable levels of performance in clinical settings.

Detection of Acute Brain Injury in Intensive Care Unit Patients on ECMO Support Using Ultra-Low-Field Portable MRI: A Retrospective Analysis Compared to Head CT.

Early detection of acute brain injury (ABI) is critical to intensive care unit (ICU) patient management and intervention to decrease major complications. Head CT (HCT) is the standard of care for the assessment of ABI in ICU patients; however, it has limited sensitivity compared to MRI. We retrospectively compared the ability of ultra-low-field portable MR (ULF-pMR) and head HCT, acquired within 24 h of each other, to detect ABI in ICU patients supported on extracorporeal membrane oxygenation (ECMO). A total of 17 adult patients (median age 55 years; 47% male) were included in the analysis. Of the 17 patients assessed, ABI was not observed on either ULF-pMR or HCT in eight patients (47%). ABI was observed in the remaining nine patients with a total of 10 events (8 ischemic, 2 hemorrhagic). Of the eight ischemic events, ULF-pMR observed all eight, while HCT only observed four events. Regarding hemorrhagic stroke, ULF-pMR observed only one of them, while HCT observed both. ULF-pMR outperformed HCT for the detection of ABI, especially ischemic injury, and may offer diagnostic advantages for ICU patients. The lack of sensitivity to hemorrhage may improve with modification of the imaging acquisition program.

Clinical Use of Bedside Portable Low-field Brain Magnetic Resonance Imaging in Patients on ECMO: The Results from Multicenter SAFE MRI ECMO Study.

Purpose: Early detection of acute brain injury (ABI) is critical for improving survival for patients with extracorporeal membrane oxygenation (ECMO) support. We aimed to evaluate the safety of ultra-low-field portable MRI (ULF-pMRI) and the frequency and types of ABI observed during ECMO support. Methods: We conducted a multicenter prospective observational study (NCT05469139) at two academic tertiary centers (August 2022-November 2023). Primary outcomes were safety and validation of ULF-pMRI in ECMO, defined as exam completion without adverse events (AEs); secondary outcomes were ABI frequency and type. Results: ULF-pMRI was performed in 50 patients with 34 (68%) on venoarterial (VA)-ECMO (11 central; 23 peripheral) and 16 (32%) with venovenous (VV)-ECMO (9 single lumen; 7 double lumen). All patients were imaged successfully with ULF-pMRI, demonstrating discernible intracranial pathologies with good quality. AEs occurred in 3 (6%) patients (2 minor; 1 serious) without causing significant clinical issues.ABI was observed in ULF-pMRI scans for 22 patients (44%): ischemic stroke (36%), intracranial hemorrhage (6%), and hypoxic-ischemic brain injury (4%). Of 18 patients with both ULF-pMRI and head CT (HCT) within 24 hours, ABI was observed in 9 patients with 10 events: 8 ischemic (8 observed on ULF-oMRI, 4 on HCT) and 2 hemorrhagic (1 observed on ULF-pMRI, 2 on HCT). Conclusions: ULF-pMRI was shown to be safe and valid in ECMO patients across different ECMO cannulation strategies. The incidence of ABI was high, and ULF-pMRI may more sensitive to ischemic ABI than HCT. ULF-pMRI may benefit both clinical care and future studies of ECMO-associated ABI.

Umbrella review and network meta-analysis of diagnostic imaging test accuracy studies in Differentiating between brain tumor progression versus pseudoprogression and radionecrosis.

PURPOSE: In this study we gathered and analyzed the available evidence regarding 17 different imaging modalities and performed network meta-analysis to find the most effective modality for the differentiation between brain tumor recurrence and post-treatment radiation effects. METHODS: We conducted a comprehensive systematic search on PubMed and Embase. The quality of eligible studies was assessed using the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) instrument. For each meta-analysis, we recalculated the effect size, sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio from the individual study data provided in the original meta-analysis using a random-effects model. Imaging technique comparisons were then assessed using NMA. Ranking was assessed using the multidimensional scaling approach and by visually assessing surface under the cumulative ranking curves. RESULTS: We identified 32 eligible studies. High confidence in the results was found in only one of them, with a substantial heterogeneity and small study effect in 21% and 9% of included meta-analysis respectively. Comparisons between MRS Cho/NAA, Cho/Cr, DWI, and DSC were most studied. Our analysis showed MRS (Cho/NAA) and 18F-DOPA PET displayed the highest sensitivity and negative likelihood ratios. 18-FET PET was ranked highest among the 17 studied techniques with statistical significance. APT MRI was the only non-nuclear imaging modality to rank higher than DSC, with statistical insignificance, however. CONCLUSION: The evidence regarding which imaging modality is best for the differentiation between radiation necrosis and post-treatment radiation effects is still inconclusive. Using NMA, our analysis ranked FET PET to be the best for such a task based on the available evidence. APT MRI showed promising results as a non-nuclear alternative.

Trial Readiness of Cavernous Malformations With Symptomatic Hemorrhage, Part I: Event Rates and Clinical Outcome.

BACKGROUND: Cerebral cavernous malformation with symptomatic hemorrhage (SH) are targets for novel therapies. A multisite trial-readiness project (https://www.clinicaltrials.gov; Unique identifier: NCT03652181) aimed to identify clinical, imaging, and functional changes in these patients. METHODS: We enrolled adult cerebral cavernous malformation patients from 5 high-volume centers with SH within the prior year and no planned surgery. In addition to clinical and imaging review, we assessed baseline, 1- and 2-year National Institutes of Health Stroke Scale, modified Rankin Scale, European Quality of Life 5D-3 L, and patient-reported outcome-measurement information system, Version 2.0. SH and asymptomatic change rates were adjudicated. Changes in functional scores were assessed as a marker for hemorrhage. RESULTS: One hundred twenty-three, 102, and 69 patients completed baseline, 1- and 2-year clinical assessments, respectively. There were 21 SH during 178.3 patient years of follow-up (11.8% per patient year). At baseline, 62.6% and 95.1% of patients had a modified Rankin Scale score of 1 and National Institutes of Health Stroke Scale score of 0 to 4, respectively, which improved to 75.4% (P=0.03) and 100% (P=0.06) at 2 years. At baseline, 74.8% had at least one abnormal patient-reported outcome-measurement information system, Version 2.0 domain compared with 61.2% at 2 years (P=0.004). The most common abnormal European Quality of Life 5D-3 L domains were pain (48.7%), anxiety (41.5%), and participation in usual activities (41.4%). Patients with prospective SH were more likely than those without SH to display functional decline in sleep, fatigue, and social function patient-reported outcome-measurement information system, Version 2.0 domains at 2 years. Other score changes did not differ significantly between groups at 2 years. The sensitivity of scores as an SH marker remained poor at the time interval assessed. CONCLUSIONS: We report SH rate, functional, and patient-reported outcomes in trial-eligible cerebral cavernous malformation with SH patients. Functional outcomes and patient-reported outcomes generally improved over 2 years. No score change was highly sensitive or specific for SH and could not be used as a primary end point in a trial.

Trial Readiness of Cavernous Malformations With Symptomatic Hemorrhage, Part II: Biomarkers and Trial Modeling.

BACKGROUND: Quantitative susceptibility mapping (QSM) and dynamic contrast-enhanced quantitative perfusion (DCEQP) magnetic resonance imaging sequences assessing iron deposition and vascular permeability were previously correlated with new hemorrhage in cerebral cavernous malformations. We assessed their prospective changes in a multisite trial-readiness project. METHODS: Patients with cavernous malformation and symptomatic hemorrhage (SH) in the prior year, without prior or planned lesion resection or irradiation were enrolled. Mean QSM and DCEQP of the SH lesion were acquired at baseline and at 1- and 2-year follow-ups. Sensitivity and specificity of biomarker changes were analyzed in relation to predefined criteria for recurrent SH or asymptomatic change. Sample size calculations for hypothesized therapeutic effects were conducted. RESULTS: We logged 143 QSM and 130 DCEQP paired annual assessments. Annual QSM change was greater in cases with SH than in cases without SH (P=0.019). Annual QSM increase by ≥6% occurred in 7 of 7 cases (100%) with recurrent SH and in 7 of 10 cases (70%) with asymptomatic change during the same epoch and 3.82× more frequently than clinical events. DCEQP change had lower sensitivity for SH and asymptomatic change than QSM change and greater variance. A trial with the smallest sample size would detect a 30% difference in QSM annual change during 2 years of follow-up in 34 or 42 subjects (1 and 2 tailed, respectively); power, 0.8, α=0.05. CONCLUSIONS: Assessment of QSM change is feasible and sensitive to recurrent bleeding in cavernous malformations. Evaluation of an intervention on QSM percent change may be used as a time-averaged difference between 2 arms using a repeated measures analysis. DCEQP change is associated with lesser sensitivity and higher variability than QSM. These results are the basis of an application for certification by the US Food and Drug Administration of QSM as a biomarker of drug effect on bleeding in cavernous malformations. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03652181.

The association between post-traumatic stress disorder (PTSD) and cognitive impairment: A systematic review of neuroimaging findings.

BACKGROUND: Accumulating evidence suggests that post-traumatic stress disorder (PTSD) may increase the risk of various types of dementia. Despite the large number of studies linking these critical conditions, the underlying mechanisms remain unclear. The past decade has witnessed an exponential increase in interest on brain imaging research to assess the neuroanatomical underpinnings of PTSD. This systematic review provides a critical assessment of available evidence of neuroimaging correlates linking PTSD to a higher risk of dementia. METHODS: The EMBASE, PubMed/MEDLINE, and SCOPUS electronic databases were systematically searched from 1980 to May 22, 2021 for original references on neuroimaging correlates of PTSD and risk of dementia. Literature search, screening of references, methodological quality appraisal of included articles as well as data extractions were independently conducted by at least two investigators. Eligibility criteria included: 1) a clear PTSD definition; 2) a subset of included participants must have developed dementia or cognitive impairment at any time point after the diagnosis of PTSD through any diagnostic criteria; and 3) brain imaging protocols [structural, molecular or functional], including whole-brain morphologic and functional MRI, and PET imaging studies linking PTSD to a higher risk of cognitive impairment/dementia. RESULTS: Overall, seven articles met eligibility criteria, comprising findings from 366 participants with PTSD. Spatially convergent structural abnormalities in individuals with PTSD and co-occurring cognitive dysfunction involved primarily the bilateral frontal (e.g., prefrontal, orbitofrontal, cingulate cortices), temporal (particularly in those with damage to the hippocampi), and parietal (e.g., superior and precuneus) regions. LIMITATIONS: A meta-analysis could not be performed due to heterogeneity and paucity of measurable data in the eligible studies. CONCLUSIONS: Our systematic review provides putative neuroimaging correlates associated with PTSD and co-occurring dementia/cognitive impairment particularly involving the hippocampi. Further research examining neuroimaging features linking PTSD to dementia are clearly an unmet need of the field. Future imaging studies should provide a better control for relevant confounders, such as the selection of more homogeneous samples (e.g., age, race, education), a proper control for co-occurring disorders (e.g., co-occurring major depressive and anxiety disorders) as well as the putative effects of psychotropic medication use. Furthermore, prospective studies examining imaging biomarkers associated with a higher rate of conversion from PTSD to dementia could aid in the stratification of people with PTSD at higher risk for developing dementia for whom putative preventative interventions could be especially beneficial.

Cavernous Angioma Symptomatic Hemorrhage (CASH) Trial Readiness II: Imaging Biomarkers and Trial Modeling.

Background: Quantitative susceptibility mapping (QSM) and dynamic contrast enhanced quantitative perfusion (DCEQP) MRI sequences assessing iron deposition and vascular permeability were previously correlated with new hemorrhage in cavernous angiomas. We assessed their prospective changes in cavernous angiomas with symptomatic hemorrhage (CASH) in a multisite trial readiness project ( clinicaltrials.gov NCT03652181 ). Methods: Patients with CASH in the prior year, without prior or planned lesion resection or irradiation were enrolled. Mean QSM and DCEQP of CASH lesion were acquired at baseline, and at 1- and 2-year follow-ups. Sensitivity and specificity of biomarker changes were analyzed in relation to predefined lesional symptomatic hemorrhage (SH) or asymptomatic change (AC). Sample size calculations for hypothesized therapeutic effects were conducted. Results: We logged 143 QSM and 130 DCEQP paired annual assessments. Annual QSM change was greater in cases with SH than in cases without SH (p= 0.019). Annual QSM increase by ≥ 6% occurred in 7 of 7 cases (100%) with recurrent SH and in 7 of 10 cases (70%) with AC during the same epoch, and 3.82 times more frequently than clinical events. DCEQP change had lower sensitivity for SH and AC than QSM change, and greater variance. A trial with smallest sample size would detect a 30% difference in QSM annual change in 34 or 42 subjects (one and two-tailed, respectively), power 0.8, alpha 0.05. Conclusions: Assessment of QSM change is feasible and sensitive to recurrent bleeding in CASH. Evaluation of an intervention on QSM percent change may be used as a time-averaged difference between 2 arms using a repeated measures analysis. DCEQP change is associated with lesser sensitivity and higher variability than QSM. These results are the basis of an application for certification by the U.S. F.D.A. of QSM as a biomarker of drug effect in CASH.

Brain Tumor Segmentation for Multi-Modal MRI with Missing Information.

Deep convolutional neural networks (DCNNs) have shown promise in brain tumor segmentation from multi-modal MRI sequences, accommodating heterogeneity in tumor shape and appearance. The fusion of multiple MRI sequences allows networks to explore complementary tumor information for segmentation. However, developing a network that maintains clinical relevance in situations where certain MRI sequence(s) might be unavailable or unusual poses a significant challenge. While one solution is to train multiple models with different MRI sequence combinations, it is impractical to train every model from all possible sequence combinations. In this paper, we propose a DCNN-based brain tumor segmentation framework incorporating a novel sequence dropout technique in which networks are trained to be robust to missing MRI sequences while employing all other available sequences. Experiments were performed on the RSNA-ASNR-MICCAI BraTS 2021 Challenge dataset. When all MRI sequences were available, there were no significant differences in performance of the model with and without dropout for enhanced tumor (ET), tumor (TC), and whole tumor (WT) (p-values 1.000, 1.000, 0.799, respectively), demonstrating that the addition of dropout improves robustness without hindering overall performance. When key sequences were unavailable, the network with sequence dropout performed significantly better. For example, when tested on only T1, T2, and FLAIR sequences together, DSC for ET, TC, and WT increased from 0.143 to 0.486, 0.431 to 0.680, and 0.854 to 0.901, respectively. Sequence dropout represents a relatively simple yet effective approach for brain tumor segmentation with missing MRI sequences.

The Cortico-Limbo-Thalamo-Cortical Circuits: An Update to the Original Papez Circuit of the Human Limbic System.

The Papez circuit, first proposed by James Papez in 1937, is a circuit believed to control memory and emotions, composed of the cingulate cortex, entorhinal cortex, parahippocampal gyrus, hippocampus, hypothalamus, and thalamus. Pursuant to James Papez, Paul Yakovlev and Paul MacLean incorporated the prefrontal/orbitofrontal cortex, septum, amygdalae, and anterior temporal lobes into the limbic system. Over the past few years, diffusion-weighted tractography techniques revealed additional limbic fiber connectivity, which incorporates multiple circuits to the already known complex limbic network. In the current review, we aimed to comprehensively summarize the anatomy of the limbic system and elaborate on the anatomical connectivity of the limbic circuits based on the published literature as an update to the original Papez circuit.

The Ribbon Sign as a Radiological Indicator of Intramedullary Spinal Cord Subependymomas.

OBJECTIVE: Intramedullary spinal cord (IMSC) subependymomas are rare World Health Organization grade 1 ependymal tumors. The potential presence of functional neural tissue within the tumor and poorly demarcated planes presents a risk to resection. Anticipating a subependymoma on preoperative imaging can inform surgical decision-making and improve patient counseling. Here, we present our experience recognizing IMSC subependymomas on preoperative magnetic resonance imaging (MRI) based on a distinctive characteristic termed the "ribbon sign." METHODS: We retrospectively reviewed preoperative MRIs of patients presenting with IMSC tumors at a large tertiary academic institution between April 2005 and January 2022. The diagnosis was confirmed histologically. The "ribbon sign" was defined as a ribbon-like structure of T2 isointense spinal cord tissue interwoven between regions of T2 hyperintense tumor. The ribbon sign was confirmed by an expert neuroradiologist. RESULTS: MRIs from 151 patients were reviewed, including 10 patients with IMSC subependymomas. The ribbon sign was demonstrated on 9 (90%) patients with histologically proven subependymomas. Other tumor types did not display the ribbon sign. CONCLUSION: The ribbon sign is a potentially distinctive imaging feature of IMSC subependymomas and indicates the presence of spinal cord tissue between eccentrically located tumors. Recognition of the ribbon sign should prompt clinicians to consider a diagnosis of subependymoma, aiding the neurosurgeon in planning the surgical approach and adjusting the surgical outcome expectation. Consequently, the risks and benefits of gross-versus subtotal resection for palliative debulking should be carefully considered and discussed with patients.

Interrater Reliability of Cervical Neural Foraminal Stenosis Using Traditional and Splayed Reconstructions: Analysis of One Hundred Scans.

OBJECTIVE: The oblique sagittal orientation of the cervical neural foramina hinders the evaluation of cervical neural foraminal stenosis (CNFS) on traditional axial and sagittal slices. Traditional image reconstruction techniques to generate oblique slices provide only a view of the foramina unilaterally. We present a simple technique for generating splayed slices that show the bilateral neuroforamina simultaneously and assess its reliability compared with traditional axial windows. METHODS: Cervical computed tomography (CT) scans from 100 patients were retrospectively collected and de-identified. The axial slices were reformatted into a curved reformat with the plane of the reformat extending across the bilateral neuroforamina. The foramina along the C2-T1 vertebral levels were assessed by 4 neuroradiologists using the axial and splayed slices. The intrarater agreement across the axial and splayed slices for a given foramen and the interrater agreement for the axial and splayed slices individually were calculated using the Cohen κ statistic. RESULTS: Interrater agreement was overall higher for the splayed slices (κ = 0.25) compared with the axial slices (κ = 0.20). The splayed slices were more likely to have fair agreement across raters compared with the axial slices. Intrarater agreement between the axial and splayed slices was poorer for residents compared with fellows. CONCLUSIONS: Splayed reconstructions showing the bilateral neuroforamina en face can be readily generated from axial CT imaging. These splayed reconstructions can improve the consistency of CNFS evaluation compared with traditional CT slices and should be considered in the workup of CNFS, particularly for less experienced readers.