Large variation in radiation dose for routine abdomen CT: reasons for excess and easy tips for reduction.

OBJECTIVE: To characterize the use and impact of radiation dose reduction techniques in actual practice for routine abdomen CT. METHODS: We retrospectively analyzed consecutive routine abdomen CT scans in adults from a large dose registry, contributed by 95 hospitals and imaging facilities. Grouping exams into deciles by, first, patient size, and second, size-adjusted dose length product (DLP), we summarized dose and technical parameters and estimated which parameters contributed most to between-protocols dose variation. Lastly, we modeled the total population dose if all protocols with mean size-adjusted DLP above 433 or 645 mGy-cm were reduced to these thresholds. RESULTS: A total of 748,846 CTs were performed using 1033 unique protocols. When sorted by patient size, patients with larger abdominal diameters had increased dose and effective mAs (milliampere seconds), even after adjusting for patient size. When sorted by size-adjusted dose, patients in the highest versus the lowest decile in size-adjusted DLP received 6.4 times the average dose (1680 vs 265 mGy-cm) even though diameter was no different (312 vs 309 mm). Effective mAs was 2.1-fold higher, unadjusted CTDIvol 2.9-fold, and phase 2.5-fold for patients in the highest versus lowest size-adjusted DLP decile. There was virtually no change in kV (kilovolt). Automatic exposure control was widely used to modulate mAs, whereas kV modulation was rare. Phase was the strongest driver of between-protocols variation. Broad adoption of optimized protocols could result in total population dose reductions of 18.6-40%. CONCLUSION: There are large variations in radiation doses for routine abdomen CT unrelated to patient size. Modification of kV and single-phase scanning could result in substantial dose reduction. CLINICAL RELEVANCE: Radiation dose-optimization techniques for routine abdomen CT are routinely under-utilized leading to higher doses than needed. Greater modification of technical parameters and number of phases could result in substantial reduction in radiation exposure to patients. KEY POINTS: • Based on an analysis of 748,846 routine abdomen CT scans in adults, radiation doses varied tremendously across patients of the same size and optimization techniques were routinely under-utilized. • The difference in observed dose was due to variation in technical parameters and phase count. Automatic exposure control was commonly used to modify effective mAs, whereas kV was rarely adjusted for patient size. Routine abdomen CT should be performed using a single phase, yet multi-phase was common. • kV modulation by patient size and restriction to a single phase for routine abdomen indications could result in substantial reduction in radiation doses using well-established dose optimization approaches.

Dose length product to effective dose coefficients in adults.

OBJECTIVES: The most accurate method for estimating patient effective dose (a principal metric for tracking patient radiation exposure) from computed tomography (CT) requires time-intensive Monte Carlo simulation. A simpler method multiplies a scalar coefficient by the widely available scanner-reported dose length product (DLP) to estimate effective dose. We developed new adult effective dose coefficients using actual patient scans and assessed their agreement with Monte Carlo simulation. METHODS: A multicenter sample of 216,906 adult CT scans was prospectively assembled in 2015-2020 from the University of California San Francisco International CT Dose Registry and the University of Florida library of computational phantoms. We generated effective dose coefficients for eight body regions, stratified by patient sex, diameter, and scanner manufacturer. We applied the new coefficients to DLPs to calculate effective doses and assess their correlations with Monte Carlo radiation transport-generated effective dose. RESULTS: Effective dose coefficients varied by body region and decreased in magnitude with increasing patient diameter. Coefficients were approximately twofold higher for torso scans in smallest compared with largest diameter categories. For example, abdomen and pelvis coefficients decreased from 0.027 to 0.013 mSv/mGy-cm between the 16-20 cm and 41+ cm categories. There were modest but consistent differences by sex and manufacturer. Diameter-based coefficients used to estimate effective dose produced strong correlations with the reference standard (Pearson correlations 0.77-0.86). The reported conversion coefficients differ from previous studies, particularly in neck CT. CONCLUSIONS: New effective dose coefficients derived from empirical clinical scans can be used to easily estimate effective dose using scanner-reported DLP. CLINICAL RELEVANCE STATEMENT: Scalar coefficients multiplied by DLP offer a simple approximation to effective dose, a key radiation dose metric. New effective dose coefficients from this study strongly correlate with gold standard, Monte Carlo-generated effective dose, and differ somewhat from previous studies. KEY POINTS: • Previous effective dose coefficients were derived from theoretical models rather than real patient data. • The new coefficients (from a large registry/phantom library) differ from previous studies. • The new coefficients offer reasonably reliable values for estimating effective dose.

The neuropathology of intimate partner violence.

Lifelong brain health consequences of traumatic brain injury (TBI) include the risk of neurodegenerative disease. Up to one-third of women experience intimate partner violence (IPV) in their lifetime, often with TBI, yet remarkably little is known about the range of autopsy neuropathologies encountered in IPV. We report a prospectively accrued case series from a single institution, the New York City Office of Chief Medical Examiner, evaluated in partnership with the Brain Injury Research Center of Mount Sinai, using a multimodal protocol comprising clinical history review, ex vivo imaging in a small subset, and comprehensive neuropathological assessment by established consensus protocols. Fourteen brains were obtained over 2 years from women with documented IPV (aged 3rd-8th decade; median, 4th) and complex histories including prior TBI in 6, nonfatal strangulation in 4, cerebrovascular, neurological, and/or psychiatric conditions in 13, and epilepsy in 7. At autopsy, all had TBI stigmata (old and/or recent). In addition, white matter regions vulnerable to diffuse axonal injury showed perivascular and parenchymal iron deposition and microgliosis in some subjects. Six cases had evidence of cerebrovascular disease (lacunes and/or chronic infarcts). Regarding neurodegenerative disease pathologies, Alzheimer disease neuropathologic change was present in a single case (8th decade), with no chronic traumatic encephalopathy neuropathologic change (CTE-NC) identified in any. Findings from this initial series then prompted similar exploration in an expanded case series of 70 archival IPV cases (aged 2nd-9th decade; median, 4th) accrued from multiple international institutions. In this secondary case series, we again found evidence of vascular and white matter pathologies. However, only limited neurodegenerative proteinopathies were encountered in the oldest subjects, none meeting consensus criteria for CTE-NC. These observations from this descriptive exploratory study reinforce a need to consider broad co-morbid and neuropathological substrates contributing to brain health outcomes in the context of IPV, some of which may be potentially modifiable.

Enhancing the brain MRI at ultra-high field systems using a meta-array structure.

BACKGROUND: The main advantage of ultra-high field (UHF) magnetic resonance neuroimaging is theincreased signal-to-noise ratio (SNR) compared with lower field strength imaging. However, the wavelength effect associated with UHF MRI results in radiofrequency (RF) inhomogeneity, compromising whole brain coverage for many commercial coils. Approaches to resolving this issue of transmit field inhomogeneity include the design of parallel transmit systems (PTx), RF pulse design, and applying passive RF shimming such as high dielectric materials. However, these methods have some drawbacks such as unstable material parameters of dielectric pads, high-cost, and complexity of PTx systems. Metasurfaces are artificial structures with a unique platform that can control the propagation of the electromagnetic (EM) waves, and they are very promising for engineering EM device. Implementation of meta-arrays enhancing MRI has been explored previously in several studies. PURPOSE: The aim of this study was to assess the effect of new meta-array technology on enhancing the brain MRI at 7T. A meta-array based on a hybrid structure consisting of an array of broadside-coupled split-ring resonators and high-permittivity materials was designed to work at the Larmor frequency of a 7 Tesla (7T) MRI scanner. When placed behind the head and neck, this construct improves the SNR in the region of the cerebellum,brainstem and the inferior aspect of the temporal lobes. METHODS: Numerical electromagnetic simulations were performed to optimize the meta-array design parameters and determine the RF circuit configuration. The resultant transmit-efficiency and signal sensitivity improvements were experimentally analyzed in phantoms followed by healthy volunteers using a 7T whole-body MRI scanner equipped with a standard one-channel transmit, 32-channel receive head coil. Efficacy was evaluated through acquisition with and without the meta-array using two basic sequences: gradient-recalled-echo (GRE) and turbo-spin-echo (TSE). RESULTS: Experimental phantom analysis confirmed two-fold improvement in the transmit efficiency and 1.4-fold improvement in the signal sensitivity in the target region. In vivo GRE and TSE images with the meta-array in place showed enhanced visualization in inferior regions of the brain, especially of the cerebellum, brainstem, and cervical spinal cord. CONCLUSION: Addition of the meta-array to commonly used MRI coils can enhance SNR to extend the anatomical coverage of the coil and improve overall MRI coil performance. This enhancement in SNR can be leveraged to obtain a higher resolution image over the same time slot or faster acquisition can be achieved with same resolution. Using this technique could improve the performance of existing commercial coils at 7T for whole brain and other applications.

Orbital Foraminal Morphometrics in Nonsyndromic Unilateral Coronal Craniosynostosis.

ABSTRACT: Nonsyndromic unilateral coronal craniosynostosis (UCS) is a rare congenital disorder that results from premature fusion of either coronal suture. The result is growth restriction across the suture, between the ipsilateral frontal and parietal bones, leading to bony dysmorphogenesis affecting the calvarium, orbit, and skull base. Prior studies have reported associations between UCS and visual abnormalities. The present study utilizes a novel geometric morphometric analysis to compare dimensions of orbital foramina on synostotic versus nonsynostotic sides in patients with UCS. Computed tomography head scans of pediatric UCS patients were converted into 3-dimensional mesh models. Anatomical borders of left and right orbital structures were plotted by a single trained team member. Dimensions between synostotic and nonsynostotic sides were measured and compared. Medical records were examined to determine prevalence of visual abnormalities in this patient cohort. Visual abnormalities were reported in 22 of the 27 UCS patients (77.8%). Astigmatism (66.7%), anisometropic amblyopia (44.4%), and motor nerve palsies (33.3%) represented the 3 most prevalent ophthalmologic abnormalities. Orbits on synostotic sides were 11.3% narrower ( P < 0.001) with 21.2% less volume ( P = 0.028) than orbits on nonsynostotic sides. However, average widths, circumferences, and areas were similar between synostotic and nonsynostotic sides upon comparison of supraorbital foramina, infraorbital foramina, optic foramina, and foramina ovalia. Therefore, previously proposed compression or distortion of vital neurovascular structures within bony orbital foramina does not seem to be a likely etiology of visual abnormalities in UCS patients. Future studies will examine the role of ocular and/or neuro-ophthalmologic pathology in this disease process.

Neuroimaging findings and neurological manifestations in hospitalized COVID-19 patients: Impact of cancer and ventilatory support status.

INTRODUCTION: Coronavirus 2019 (COVID-19) is known to affect the central nervous system. Neurologic morbidity associated with COVID-19 is commonly attributed to sequelae of some combination of thrombotic and inflammatory processes. The aim of this retrospective observational study was to evaluate neuroimaging findings in hospitalized COVID-19 patients with neurological manifestations in cancer versus non-cancer patients, and in patients with versus without ventilatory support (with ventilatory support defined as including patients with intubation and noninvasive ventilation). Cancer patients are frequently in an immunocompromised or prothrombotic state with side effects from chemotherapy and radiation that may cause neurological issues and increase vulnerability to systemic illness. We wanted to determine whether neurological and/or neuroimaging findings differed between patients with and without cancer. METHODS: Eighty adults (44 male, 36 female, 64.5 ±14 years) hospitalized in the Mount Sinai Health System in New York City between March 2020 and April 2021 with reverse-transcriptase polymerase chain reaction-confirmed COVID-19 underwent magnetic resonance imaging (MRI) during their admissions. The cohort consisted of four equal subgroups based on cancer and ventilatory support status. Clinical and imaging data were acquired and analyzed. RESULTS: Neuroimaging findings included non-ischemic parenchymal T2/FLAIR signal hyperintensities (36.3%), acute/subacute infarcts (26.3%), chronic infarcts (25.0%), microhemorrhages (23.8%), chronic macrohemorrhages (10.0%), acute macrohemorrhages (7.5%), and encephalitis-like findings (7.5%). There were no significant differences in neuroimaging findings between cancer and non-cancer subgroups. Clinical neurological manifestations varied. The most common was encephalopathy (77.5%), followed by impaired responsiveness/coma (38.8%) and stroke (26.3%). There were significant differences between patients with versus without ventilatory support. Encephalopathy and impaired responsiveness/coma were more prevalent in patients with ventilatory support (p = 0.02). Focal weakness was more frequently seen in patients without ventilatory support (p = 0.01). DISCUSSION: This study suggests COVID-19 is associated with neurological manifestations that may be visible with brain imaging techniques such as MRI. In our COVID-19 cohort, there was no association between cancer status and neuroimaging findings. Future studies might include more prospectively enrolled systematically characterized patients, allowing for more rigorous statistical analysis.

Dose length product to effective dose coefficients in children.

BACKGROUND: The most accurate method for estimating effective dose (the most widely understood metric for tracking patient radiation exposure) from computed tomography (CT) requires time-intensive Monte Carlo simulation. A simpler method multiplies a scalar coefficient by the widely available scanner-reported dose length product (DLP) to estimate effective dose. OBJECTIVE: Develop pediatric effective dose coefficients and assess their agreement with Monte Carlo simulation. MATERIALS AND METHODS: Multicenter, population-based sample of 128,397 pediatric diagnostic CT scans prospectively assembled in 2015-2020 from the University of California San Francisco International CT Dose Registry and the University of Florida library of highly realistic hybrid computational phantoms. We generated effective dose coefficients for seven body regions, stratified by patient age, diameter, and scanner manufacturer. We applied the new coefficients to DLPs to calculate effective doses and assessed their correlations with Monte Carlo radiation transport-generated effective doses. RESULTS: The reported effective dose coefficients, generally higher than previous studies, varied by body region and decreased in magnitude with increasing age. Coefficients were approximately 4 to 13-fold higher (across body regions) for patients <1 year old compared with patients 15-21 years old. For example, head CT (54% of scans) dose coefficients decreased from 0.039 to 0.003 mSv/mGy-cm in patients <1 year old vs. 15-21 years old. There were minimal differences by manufacturer. Using age-based conversion coefficients to estimate effective dose produced moderate to strong correlations with Monte Carlo results (Pearson correlations 0.52-0.80 across body regions). CONCLUSIONS: New pediatric effective dose coefficients update existing literature and can be used to easily estimate effective dose using scanner-reported DLP.

Third Ventricular Subependymomas: Clinical Features and Outcomes Over Two Decades.

BACKGROUND: Subependymomas are uncommon, benign slow-growing neoplasms of the central nervous system preferentially arising within the fourth and lateral ventricles. Third ventricle involvement has been described rarely. The aim of this study is to provide the first systematic review of third ventricular subependymomas (TVSE) by analyzing all reported cases over 2 decades and describing a case example. METHODS: MEDLINE and Embase databases were searched for the 20 years ending January 1, 2022, using relevant MeSH and non-MeSH terms, including "subependymoma" and "third ventricle." Methodology followed PRISMA guidelines. RESULTS: Of 804 identified studies, 131 met inclusion eligibility. The literature yielded 17 patients with TVSE plus our example (18 total). Of these patients, 83% (15/18) presented in adulthood (average age, 42 ± 19 years), of whom 73% were women. The pediatric cohort age was 5 ± 1 years, 67% (4/6) of whom were girls. The most common presenting symptom in both cohorts was headache (80%), followed by memory disturbances and vomitus. In adults, symptomatic tumors were approached by open craniotomy in all but 1 case, most using a transcallosal approach. Gross total resection was obtained in 73%. A ventriculoperitoneal shunt was inserted in 2/15 adult and 4/6 pediatric patients. Overall, both cohorts showed symptomatic improvement without disease recurrence. One patient died perioperatively. CONCLUSIONS: Subependymomas should be considered in the differential diagnosis of third ventricular tumors. The clinical presentation of TVSE mainly parallels hydrocephalus symptoms and, hence, awareness is of vital importance for timely treatment. The surgical goal should be gross total resection, which can be curative and offers greatest clinical improvement across the population.

Stress-related reduction of hippocampal subfield volumes in major depressive disorder: A 7-Tesla study.

Background: Major depressive disorder (MDD) is a prevalent health problem with complex pathophysiology that is not clearly understood. Prior work has implicated the hippocampus in MDD, but how hippocampal subfields influence or are affected by MDD requires further characterization with high-resolution data. This will help ascertain the accuracy and reproducibility of previous subfield findings in depression as well as correlate subfield volumes with MDD symptom scores. The objective of this study was to assess volumetric differences in hippocampal subfields between MDD patients globally and healthy controls (HC) as well as between a subset of treatment-resistant depression (TRD) patients and HC using automatic segmentation of hippocampal subfields (ASHS) software and ultra-high field MRI. Methods: Thirty-five MDD patients and 28 HC underwent imaging using 7-Tesla MRI. ASHS software was applied to the imaging data to perform automated hippocampal segmentation and provide volumetrics for analysis. An exploratory analysis was also performed on associations between symptom scores for diagnostic testing and hippocampal subfield volumes. Results: Compared to HC, MDD and TRD patients showed reduced right-hemisphere CA2/3 subfield volume (p = 0.01, η 2 = 0.31 and p = 0.3, η 2 = 0.44, respectively). Additionally, negative associations were found between subfield volumes and life-stressor checklist scores, including left CA1 (p = 0.041, f 2 = 0.419), left CA4/DG (p = 0.010, f 2 = 0.584), right subiculum total (p = 0.038, f 2 = 0.354), left hippocampus total (p = 0.015, f 2 = 0.134), and right hippocampus total (p = 0.034, f 2 = 0.110). Caution should be exercised in interpreting these results due to the small sample size and low power. Conclusion: Determining biomarkers for MDD and TRD pathophysiology through segmentation on high-resolution MRI data and understanding the effects of stress on these regions can enable better assessment of biological response to treatment selection and may elucidate the underlying mechanisms of depression.

AI software detection of large vessel occlusion stroke on CT angiography: a real-world prospective diagnostic test accuracy study.

BACKGROUND: Artificial intelligence (AI) software is increasingly applied in stroke diagnostics. However, the actual performance of AI tools for identifying large vessel occlusion (LVO) stroke in real time in a real-world setting has not been fully studied. OBJECTIVE: To determine the accuracy of AI software in a real-world, three-tiered multihospital stroke network. METHODS: All consecutive head and neck CT angiography (CTA) scans performed during stroke codes and run through an AI software engine (Viz LVO) between May 2019 and October 2020 were prospectively collected. CTA readings by radiologists served as the clinical reference standard test and Viz LVO output served as the index test. Accuracy metrics were calculated. RESULTS: Of a total of 1822 CTAs performed, 190 occlusions were identified; 142 of which were internal carotid artery terminus (ICA-T), middle cerebral artery M1, or M2 locations. Accuracy metrics were analyzed for two different groups: ICA-T and M1 ±M2. For the ICA-T/M1 versus the ICA-T/M1/M2 group, sensitivity was 93.8% vs 74.6%, specificity was 91.1% vs 91.1%, negative predictive value was 99.7% vs 97.6%, accuracy was 91.2% vs 89.8%, and area under the curve was 0.95 vs 0.86, respectively. Detection rates for ICA-T, M1, and M2 occlusions were 100%, 93%, and 49%, respectively. As expected, the algorithm offered better detection rates for proximal occlusions than for mid/distal M2 occlusions (58% vs 28%, p=0.03). CONCLUSIONS: These accuracy metrics support Viz LVO as a useful adjunct tool in stroke diagnostics. Fast and accurate diagnosis with high negative predictive value mitigates missing potentially salvageable patients.

The Knosp Criteria Revisited: 3-Dimensional Volumetric Analysis as a Predictive Tool for Extent of Resection in Complex Endoscopic Pituitary Surgery.

BACKGROUND: The Knosp criteria have been the historical standard for predicting cavernous sinus invasion, and therefore extent of surgical resection, of pituitary macroadenomas. Few studies have sought to reappraise the utility of this tool after recent advances in visualization and modeling of tumors in complex endoscopic surgery. OBJECTIVE: To evaluate our proposed alternative method, using 3-dimensional (3D) volumetric imaging, and whether it can better predict extent of resection in nonfunctional pituitary adenomas. METHODS: Patients who underwent endoscopic transsphenoidal resection of pituitary macroadenomas at our institution were reviewed. Information was collected on neurological, endocrine, and visual function. Volumetric segmentation was performed using 3D Slicer software. Relationship of tumor volume, clinical features, and Knosp grade on extent of resection was examined. RESULTS: One hundred forty patients were identified who had transsphenoidal resection of nonfunctional pituitary adenomas. Macroadenomas had a median volume of 6 cm 3 (IQR 3.4-8.7), and 17% had a unilateral Knosp grade of at least 3B. On multiple logistic regression, only smaller log-transformed preoperative tumor volume was independently associated with increased odds of gross total resection (GTR; odds ratio: 0.27, 95% CI: 0.07-0.89, P < .05) when controlling for tumor proliferative status, age, and sex (area under the curve 0.67). The Knosp criteria did not independently predict GTR in this cohort ( P > .05, area under the curve 0.46). CONCLUSION: Increasing use of volumetric 3D imaging may better anticipate extent of resection compared with the Knosp grade metric and may have a greater positive predictive value for GTR. More research is needed to validate these findings and implement them using automated methods.

Ventral tegmental area integrity measured with high-resolution 7-Tesla MRI relates to motivation across depression and anxiety diagnoses.

The ventral tegmental area (VTA) is one of the major sources of dopamine in the brain and has been associated with reward prediction, error-based reward learning, volitional drive and anhedonia. However, precise anatomical investigations of the VTA have been prevented by the use of standard-resolution MRI, reliance on subjective manual tracings, and lack of quantitative measures of dopamine-related signal. Here, we combine ultra-high field 400 µm3 quantitative MRI with dopamine-related signal mapping, and a mixture of machine learning and supervised computational techniques to delineate the VTA in a transdiagnostic sample of subjects with and without depression and anxiety disorders. Subjects also underwent cognitive testing to measure intrinsic and extrinsic motivational tone. Fifty-one subjects were scanned in total, including healthy control (HC) and mood/anxiety (MA) disorder subjects. MA subjects had significantly larger VTA volumes compared to HC but significantly lower signal intensity within VTA compared to HC, indicating reduced structural integrity of the dopaminergic VTA. Interestingly, while VTA integrity did not significantly correlate with self-reported depression or anxiety symptoms, it was correlated with an objective cognitive measure of extrinsic motivation, whereby lower VTA integrity was associated with lower motivation. This is the first study to demonstrate a computational pipeline for detecting and delineating the VTA in human subjects with 400 µm3 resolution. We highlight the use of objective transdiagnostic measures of cognitive function that link neural integrity to behavior across clinical and non-clinical groups.

Neuropathology of Pediatric SARS-CoV-2 Infection in the Forensic Setting: Novel Application of Ex Vivo Imaging in Analysis of Brain Microvasculature.

Two years into the COVID-19 pandemic, there are few published accounts of postmortem SARS-CoV-2 pathology in children. We report 8 such cases (4 infants aged 7-36 weeks, 4 children aged 5-15 years). Four underwent ex vivo magnetic resonance neuroimaging, to assist in identification of subtle lesions related to vascular compromise. All infants were found unresponsive (3 in unsafe sleeping conditions); all but 1 had recent rhinitis and/or influenza-like illness (ILI) in the family; 1 had history of sickle cell disease. Ex vivo neuroimaging in 1 case revealed white matter (WM) signal hyperintensity and diffuse exaggeration of perivascular spaces, corresponding microscopically to WM mineralization. Neurohistology in the remaining 3 infants variably encompassed WM gliosis and mineralization; brainstem gliosis; perivascular vacuolization; perivascular lymphocytes and brainstem microglia. One had ectopic hippocampal neurons (with pathogenic variant in DEPDC5). Among the children, 3 had underlying conditions (e.g., obesity, metabolic disease, autism) and all presented with ILI. Three had laboratory testing suggesting multisystem inflammatory syndrome (MIS-C). Two were hospitalized for critical care including mechanical ventilation and extracorporeal membrane oxygenation (ECMO); one (co-infected with adenovirus) developed right carotid stroke ipsilateral to the ECMO cannula and the other required surgery for an ingested foreign body. Autopsy findings included: acute lung injury in 3 (1 with microthrombi); and one each with diabetic ketoacidosis and cardiac hypertrophy; coronary and cerebral arteritis and aortitis, resembling Kawasaki disease; and neuronal storage and enlarged fatty liver. All 4 children had subtle meningoencephalitis, focally involving the brainstem. On ex vivo neuroimaging, 1 had focal pontine susceptibility with corresponding perivascular inflammation/expanded perivascular spaces on histopathology. Results suggest SARS-CoV-2 in infants may present as sudden unexpected infant death, while in older children, signs and symptoms point to severe disease. Underlying conditions may predispose to fatal outcomes. As in adults, the neuropathologic changes may be subtle, with vascular changes such as perivascular vacuolization and gliosis alongside sparse perivascular lymphocytes. Detection of subtle vascular pathology is enhanced by ex vivo neuroimaging. Additional analysis of the peripheral/autonomic nervous system and investigation of co-infection in children with COVID-19 is necessary to understand risk for cardiovascular collapse/sudden death.

Perivascular spaces as a marker of psychological trauma in depression: A 7-Tesla MRI study.

INTRODUCTION: Emerging evidence in depression suggests that blood-brain barrier (BBB) breakdown and elevated inflammatory cytokines in states of persistent stress or trauma may contribute to the development of symptoms. Signal-to-noise ratio afforded by ultra-high field MRI may aid in the detection of maladaptations of the glymphatic system related to BBB integrity that may not be visualized at lower field strengths. METHODS: We investigated the link between glymphatic neuroanatomy via perivascular spaces (PVS) and trauma experience in patients with major depressive disorder (MDD) and in healthy controls using 7-Tesla MRI and a semi-automated segmentation algorithm. RESULTS: After controlling for age and gender, the number of traumatic events was correlated with total PVS volume in MDD patients (r = 0.50, p = .028) and the overall population (r = 0.34, p = .024). The number of traumatic events eliciting horror was positively correlated with total PVS volume in MDD patients (r = 0.50, p = .030) and the overall population (r = 0.32, p = .023). Age correlated positively with PVS count, PVS total volume, and PVS density in all participants (r > 0.35, p < .01). CONCLUSIONS: These results suggest a relationship between glymphatic dysfunction related to BBB integrity and psychological trauma, and that glymphatic impairment may play a role in trauma-related symptomatology.

Quantification of brain age using high-resolution 7 tesla MR imaging and implications for patients with epilepsy.

Purpose: Epilepsy patients exhibit morphological differences on neuroimaging compared to age-matched healthy controls, including cortical and sub-cortical volume loss and altered gray-white matter ratios. The objective was to develop a model of normal aging using the 7T MRIs of healthy controls. This model can then be used to determine if the changes in epilepsy patients resemble the changes seen in aging, and potentially give a marker for the severity of those changes. Methods: Sixty-nine healthy controls (24F/45M, mean age 36.5 ± 10.5 years) and forty-four epilepsy patients (24F/20M, 33.2 ± 9.9 years) non-lesional at 3T were scanned with volumetric T1-MPRAGE at 7T. These images were segmented and quantified using FreeSurfer. A linear regression-based model trained on healthy controls was developed to predict ages using derived imaging features among the epilepsy patient cohort. The model used 114 features with significant linear correlation with age. Results: The regression-based model estimated brain age with mean absolute error (MAE) of 6.6 years among controls. Comparable prediction accuracy of 6.9 years MAE was seen epilepsy patients. T-test of mean absolute error showed no difference in the prediction accuracy with controls and epilepsy patients (p = 0.68). However, average signed error showed elevated (+5.0 years, p = 0.0007) predicted age differences (PAD; brain-PAD=, predicted minus biological age) among epilepsy patients. Morphological metrics in the medial temporal lobe were major contributors to PAD. Additionally, patients with seizure frequency greater than once a week showed significantly elevated brain-PAD (+8.2 ± 5.3 years, n = 13) compared to patients with lower seizure frequency (3.7 ± 6.5 years, n = 31, p = 0.033). Major conclusions: Morphological patterns suggestive of premature aging were observed in non-lesional epilepsy patients vs. controls and in high seizure frequency patients vs. low frequency patients. Modeling brain age with 7T MRI may provide a sensitive imaging marker to assess the differential effects of the aging process in diseases such as epilepsy.

Semi-automated Segmentation and Quantification of Perivascular Spaces at 7 Tesla in COVID-19.

While COVID-19 is primarily considered a respiratory disease, it has been shown to affect the central nervous system. Mounting evidence shows that COVID-19 is associated with neurological complications as well as effects thought to be related to neuroinflammatory processes. Due to the novelty of COVID-19, there is a need to better understand the possible long-term effects it may have on patients, particularly linkage to neuroinflammatory processes. Perivascular spaces (PVS) are small fluid-filled spaces in the brain that appear on MRI scans near blood vessels and are believed to play a role in modulation of the immune response, leukocyte trafficking, and glymphatic drainage. Some studies have suggested that increased number or presence of PVS could be considered a marker of increased blood-brain barrier permeability or dysfunction and may be involved in or precede cascades leading to neuroinflammatory processes. Due to their size, PVS are better detected on MRI at ultrahigh magnetic field strengths such as 7 Tesla, with improved sensitivity and resolution to quantify both concentration and size. As such, the objective of this prospective study was to leverage a semi-automated detection tool to identify and quantify differences in perivascular spaces between a group of 10 COVID-19 patients and a similar subset of controls to determine whether PVS might be biomarkers of COVID-19-mediated neuroinflammation. Results demonstrate a detectable difference in neuroinflammatory measures in the patient group compared to controls. PVS count and white matter volume were significantly different in the patient group compared to controls, yet there was no significant association between PVS count and symptom measures. Our findings suggest that the PVS count may be a viable marker for neuroinflammation in COVID-19, and other diseases which may be linked to neuroinflammatory processes.

Craniofacial Dysmorphology in Infants With Non-Syndromic Unilateral Coronal Craniosynostosis.

BACKGROUND: Unilateral coronal craniosynostosis (UCS) is a congenital disorder resulting from the premature suture fusion, leading to complex primary and compensatory morphologic changes in the shape of not only the calvarium and but also into the skull base. This deformity typically requires surgery to correct the shape of the skull and prevent neurologic sequelae, including increased intracranial pressure, sensory deficits, and cognitive impairment. METHODS: The present multicenter study sought to reverse-engineer the bone dysmorphogenesis seen in non-syndromic UCS using a geometric morphometric approach. Computed tomography scans for 26 non-syndromic UCS patients were converted to three-dimensional mesh models. Two hundred thirty-six unique anatomical landmarks and semi-landmarked curves were then plotted on each model, creating wireframe representations of the Patients' skulls. RESULTS: Generalized Procrustes superimposition, Principal Component Analysis, and heatmaps identified significant superior displacement of the ipsilateral orbit ("harlequin" eye deformity), anterior displacement of the ear ipsilateral to the fused coronal suture, acute deviation of midline skull base structures ipsilateral to the fused coronal suture and flattening of the parietal bone and associated failure to expand superiorly. CONCLUSIONS: The described technique illustrates the impact of premature coronal suture fusion on the development of the entire skull and proposes how bone dysmorphology contributes to the Patients' neurologic sequelae. By bridging novel basic science methodologies with clinical research, the present study quantitatively describes craniofacial development and bone dysmorphogenesis.