A cross-sectional study to test equivalence of low- versus intermediate-flip angle dynamic susceptibility contrast MRI measures of relative cerebral blood volume in patients with high-grade gliomas at 1.5 Tesla field strength.

Introduction: 1.5 Tesla (1.5T) remain a significant field strength for brain imaging worldwide. Recent computer simulations and clinical studies at 3T MRI have suggested that dynamic susceptibility contrast (DSC) MRI using a 30° flip angle ("low-FA") with model-based leakage correction and no gadolinium-based contrast agent (GBCA) preload provides equivalent relative cerebral blood volume (rCBV) measurements to the reference-standard acquisition using a single-dose GBCA preload with a 60° flip angle ("intermediate-FA") and model-based leakage correction. However, it remains unclear whether this holds true at 1.5T. The purpose of this study was to test this at 1.5T in human high-grade glioma (HGG) patients. Methods: This was a single-institution cross-sectional study of patients who had undergone 1.5T MRI for HGG. DSC-MRI consisted of gradient-echo echo-planar imaging (GRE-EPI) with a low-FA without preload (30°/P-); this then subsequently served as a preload for the standard intermediate-FA acquisition (60°/P+). Both normalized (nrCBV) and standardized relative cerebral blood volumes (srCBV) were calculated using model-based leakage correction (C+) with IBNeuro™ software. Whole-enhancing lesion mean and median nrCBV and srCBV from the low- and intermediate-FA methods were compared using the Pearson's, Spearman's and intraclass correlation coefficients (ICC). Results: Twenty-three HGG patients composing a total of 31 scans were analyzed. The Pearson and Spearman correlations and ICCs between the 30°/P-/C+ and 60°/P+/C+ acquisitions demonstrated high correlations for both mean and median nrCBV and srCBV. Conclusion: Our study provides preliminary evidence that for HGG patients at 1.5T MRI, a low FA, no preload DSC-MRI acquisition can be an appealing alternative to the reference standard higher FA acquisition that utilizes a preload.

Disparities in the Surgical Treatment of Cerebrovascular Pathologies: A Contemporary Systematic Review.

INTRODUCTION: This systematic review analyzes contemporary literature on racial/ethnic, insurance, and socioeconomic disparities within cerebrovascular surgery in the United States to determine areas for improvement. METHODS: We conducted an electronic database search of literature published between January 1990 and July 2020 using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for studies analyzing a racial/ethnic, insurance, or socioeconomic disparity within adult cerebrovascular surgery. RESULTS: Of 2873 articles screened for eligibility by title and abstract, 970 underwent full-text independent review by 3 authors. Twenty-seven additional articles were identified through references to generate a final list of 47 included studies for analysis. Forty-six were retrospective reviews and 1 was a prospective observational cohort study, thereby comprising Levels III and IV of evidence. Studies investigated carotid artery stenting (11/47, 23%), carotid endarterectomy (22/47, 46.8%), mechanical thrombectomy (8/47, 17%), and endovascular aneurysm coiling or surgical aneurysm clipping (20/47, 42.6%). Minority and underinsured patients were less likely to receive surgical treatment. Non-White patients were more likely to experience a postoperative complication, although this significance was lost in some studies using multivariate analyses to account for complication risk factors. White and privately insured patients generally experienced shorter length of hospital stay, had lower rates of in-hospital mortality, and underwent routine discharge. Twenty-five papers (53%) reported no disparities within at least one examined metric. CONCLUSIONS: This comprehensive contemporary systematic review demonstrates the existence of disparity gaps within the field of adult cerebrovascular surgery. It highlights the importance of continued investigation into sources of disparity and efforts to promote equity within the field.

Disparities in the Surgical Treatment of Adult Spine Diseases: A Systematic Review.

BACKGROUND: Our goal was to systematically review the literature on racial/ethnic, insurance, and socioeconomic disparities in adult spine surgery in the United States and analyze potential areas for improvement. METHODS: We conducted a database search of literature published between January 1990 and July 2020 using PRISMA guidelines for all studies investigating a disparity in any aspect of adult spine surgery care analyzed based on race/ethnicity, insurance status/payer, or socioeconomic status (SES). RESULTS: Of 2679 articles identified through database searching, 775 were identified for full-text independent review by 3 authors, from which a final list of 60 studies were analyzed. Forty-three studies analyzed disparities based on patient race/ethnicity, 32 based on insurance status, and 8 based on SES. Five studies assessed disparities in access to care, 15 examined surgical treatment, 35 investigated in-hospital outcomes, and 25 explored after-discharge outcomes. Minority patients were less likely to undergo surgery but more likely to receive surgery from a low-volume provider and experience postoperative complications. White and privately insured patients generally had shorter hospital length of stay, were more likely to undergo favorable/routine discharge, and had lower rates of in-hospital mortality. After discharge, white patients reported better outcomes than did black patients. Thirty-three studies (55%) reported no disparities within at least 1 examined metric. CONCLUSIONS: This comprehensive systematic review underscores ongoing potential for health care disparities among adult patients in spinal surgery. We show a need for continued efforts to promote equity and cultural competency within neurologic surgery.

Systematic Review of Racial, Socioeconomic, and Insurance Status Disparities in Neurosurgical Care for Intracranial Tumors.

BACKGROUND: The impact of race, socioeconomic status (SES), insurance status, and other social metrics on the outcomes of patients with intracranial tumors has been reported in several studies. However, these findings have not been comprehensively summarized. METHODS: We conducted a PRISMA systematic review of all published articles between 1990 and 2020 that analyzed intracranial tumor disparities, including race, SES, insurance status, and safety-net hospital status. Outcomes measured include access, standards of care, receipt of surgery, extent of resection, mortality, complications, length of stay (LOS), discharge disposition, readmission rate, and hospital charges. RESULTS: Fifty-five studies were included. Disparities in mortality were reported in 27 studies (47%), showing minority status and lower SES associated with poorer survival outcomes in 14 studies (52%). Twenty-seven studies showed that African American patients had worse outcomes across all included metrics including mortality, rates of surgical intervention, extent of resection, LOS, discharge disposition, and complication rates. Thirty studies showed that privately insured patients and patients with higher SES had better outcomes, including lower mortality, complication, and readmission rates. Six studies showed that worse outcomes were associated with treatment at safety-net and/or low-volume hospitals. The influence of Medicare or Medicaid status, or inequities affecting other minorities, was less clearly delineated. Ten studies (18%) were negative for evidence of disparities. CONCLUSIONS: Significant disparities exist among patients with intracranial tumors, particularly affecting patients of African American race and lower SES. Efforts at the hospital, state, and national level must be undertaken to identify root causes of these issues.

Systematic Review of Racial, Socioeconomic, and Insurance Status Disparities in the Treatment of Pediatric Neurosurgical Diseases in the United States.

BACKGROUND: Increasing light is being shed on how race, insurance, and socioeconomic status (SES) may be related to outcomes from disease in the United States. To better understand the impact of these health care disparities in pediatric neurosurgery, we performed a systematic review of the literature. METHODS: We conducted a systematic review using PRISMA guidelines and MeSH terms involving neurosurgical conditions and racial, ethnic, and SES disparities. Three independent reviewers screened articles and analyzed texts selected for full analysis. RESULTS: Thirty-eight studies were included in the final analysis, of which all but 2 were retrospective database reviews. Thirty-four studies analyzed race, 22 analyzed insurance status, and 13 analyzed SES/income. Overall, nonwhite patients, patients with public insurance, and patients from lower SES were shown to have reduced access to treatment and greater rates of adverse outcomes. Nonwhite patients were more likely to present at an older age with more severe disease, less likely to undergo surgery at a high-volume surgical center, and more likely to experience postoperative morbidity and mortality. Underinsured and publicly insured patients were more likely to experience delay in surgical referral, less likely to undergo surgical treatment, and more likely to experience inpatient mortality. CONCLUSIONS: Health care disparities are present within multiple populations of patients receiving pediatric neurosurgical care. This review highlights the need for continued investigation into identifying and addressing health care disparities in pediatric neurosurgery patients.

Prevalence Rate of Coexisting Rathke Cleft Cysts and Pineal Cysts: A Multicenter Cross-Sectional Study.

BACKGROUND: Rathke cleft cysts (RCCs) are benign sellar lesions originating from remnants of primitive ectoderm. They have not been previously linked to other cystic lesions, such as pineal cysts (PCs). Our objective was to perform a multicenter cross-sectional neuroimaging study to examine prevalence rates of coexisting RCC and PC. METHODS: We retrospectively queried prospectively maintained, institutional review board-approved, databases from the authors' centers. All patients undergoing transsphenoidal surgery for RCC between the years of 2011 and 2020 were included for analysis. Preoperative magnetic resonance imaging was reviewed to identify the coexistence of a PC. Patient demographics and neuroimaging characteristics were recorded. A control cohort comprised of 100 age- and sex-matched patients with nonfunctional pituitary adenoma (NFPA) who also underwent surgical intervention was utilized. RESULTS: Eighty-four patients with RCC were identified for analysis. A coexistent PC was identified in 40.5% (n = 34) of patients with RCC compared with 14.3% (n = 12) in the NFPA cohort (P < 0.001). There was no significant difference in PC size between patients with RCC and PA (8 vs. 8.8 mm, respectively; P = 0.77). Although the majority (85.7%; n = 72) of the RCC cohort were female patients, there was no sex predominance with respect to coexisting PC in either the RCC or PA cohort. CONCLUSIONS: This is the first study to report an increased prevalence of coexisting PC and RCC, possibly because of an embryologic link or other propensity for intracranial cyst formation. Additional studies in more generalizable populations can further explore the relation between RCC and PC, or other cyst formation.

Nucleus Accumbens Cell Type- and Input-Specific Suppression of Unproductive Reward Seeking.

The nucleus accumbens (NAc) contributes to behavioral inhibition and compulsions, but circuit mechanisms are unclear. Recent evidence suggests that amygdala and thalamic inputs exert opposing control over behavior, much like direct and indirect pathway output neurons. Accordingly, opponent processes between these NAc inputs or cell types may underlie efficient reward seeking. We assess the contributions of these circuit elements to mouse operant behavior during recurring conditions when reward is and is not available. Although direct pathway stimulation is rewarding and indirect pathway stimulation aversive, the activity of both cell types is elevated during periods of behavioral suppression, and the inhibition of either cell-type selectively increases unproductive reward seeking. Amygdala and thalamic inputs are also necessary for behavioral suppression, even though they both support self-stimulation and innervate different NAc subregions. These data suggest that efficient reward seeking relies on complementary activity across NAc cell types and inputs rather than opponent processes between them.

Hippocampal Input to the Nucleus Accumbens Shell Enhances Food Palatability.

BACKGROUND: Insight into the neural basis of hedonic processing has come from studies of food palatability in rodents. Pharmacological manipulations of the nucleus accumbens shell (NAcSh) have repeatedly been demonstrated to increase hedonic taste reactivity, yet the contribution of specific NAcSh circuit components is unknown. METHODS: Bidirectional optogenetic manipulations were targeted to the principal NAcSh projection neurons and afferent pathways in mice during free feeding assays. Number of licks per bout of consumption was used as a measure of food palatability as it was confirmed to track sucrose concentration and subjective flavor preferences. RESULTS: Photoinhibition of NAcSh neurons, whether general or cell-type specific, was found to alter consumption without affecting its hedonic impact. Among the principal excitatory afferent pathways, we showed that ventral hippocampal (vHipp) input alone enhances palatability upon low-frequency photostimulation time-locked to consumption. This enhancement in palatability was independent of opioid signaling and not recapitulated by NAcSh or dopamine neuron photostimulation. We further demonstrated that vHipp input photostimulation is sufficient to condition a flavor preference, while its inhibition impedes sucrose-driven flavor preference conditioning. CONCLUSIONS: These results demonstrate a novel contribution of vHipp-NAcSh pathway activity to palatability that may relate to its innervation of a particular region or neuronal ensemble in the NAcSh. These findings are consistent with the evidence that vHipp-NAcSh activity is relevant to the pathophysiology of anhedonia and depression as well as the increasing appreciation of hippocampal involvement in people's food pleasantness ratings, hunger, and weight.

Cue-Evoked Dopamine Neuron Activity Helps Maintain but Does Not Encode Expected Value.

Cue-evoked midbrain dopamine (DA) neuron activity reflects expected value, but its influence on reward assessment is unclear. In mice performing a trial-based operant task, we test if bidirectional manipulations of cue or operant-associated DA neuron activity drive learning as a result of under- or overexpectation of reward value. We target optogenetic manipulations to different components of forced trials, when only one lever is presented, and assess lever biases on choice trials in the absence of photomanipulation. Although lever biases are demonstrated to be flexible and sensitive to changes in expected value, augmentation of cue or operant-associated DA signaling does not significantly alter choice behavior, and blunting DA signaling during any component of the forced trials reduces choice trial responses on the associated lever. These data suggest cue-evoked DA helps maintain cue-value associations but does not encode expected value as to set the benchmark against which received reward is judged.

One-pot synthesis of epoxides from benzyl alcohols and aldehydes.

A one-pot synthesis of epoxides from commercially available benzyl alcohols and aldehydes is described. The reaction proceeds through in situ generation of sulfonium salts from benzyl alcohols and their subsequent deprotonation for use in Corey-Chaykovsky epoxidation of aldehydes. The generality of the method is exemplified by the synthesis of 34 epoxides that were made from an array of electronically and sterically varied alcohols and aldehydes.

Coordinated Reductions in Excitatory Input to the Nucleus Accumbens Underlie Food Consumption.

Reward-seeking behavior is regulated by a diverse collection of inputs to the nucleus accumbens (NAc). The information encoded in each excitatory afferent to the NAc is unknown, in part because it is unclear when these pathways are active in relation to behavior. Here we compare the activity profiles of amygdala, hippocampal, and thalamic inputs to the NAc shell in mice performing a cued reward-seeking task using GCaMP-based fiber photometry. We find that the rostral and caudal ends of the NAc shell are innervated by distinct but intermingled populations of forebrain neurons that exhibit divergent feeding-related activity. In the rostral NAc shell, a coordinated network-wide reduction in excitatory drive correlates with feeding, and reduced input from individual pathways is sufficient to promote it. Overall, the data suggest that pathway-specific input activity at a population level may vary more across the NAc than between pathways.