Longitudinal changes in the US emergency department use of advanced neuroimaging in the mechanical thrombectomy era.

PURPOSE: To describe ED neuroimaging trends across the time-period spanning the early adoption of endovascular therapy for acute stroke (2013-2018). MATERIALS AND METHODS: We performed a retrospective, cross-sectional study of ED visits using the 2013-2018 National Emergency Department Sample, a 20% sample of ED encounters in the United States. Neuroimaging use was determined by Common Procedural Terminology (CPT) code for non-contrast head CT (NCCT), CT angiography head (CTA), CT perfusion (CTP), and MRI brain (MRI) in non-admitted ED patients. Data was analyzed according to sampling weights and imaging rates were calculated per 100,000 ED visits. Multivariate logistic regression analysis was performed to identify hospital-level factors associated with imaging utilization. RESULTS: Study population comprised 571,935,906 weighted adult ED encounters. Image utilization increased between 2013 and 2018 for all modalities studied, although more pronounced in CTA (80.24/100,000 ED visits to 448.26/100,000 ED visits (p < 0.001)) and CTP (1.75/100,000 ED visits to 28.04/100,000 ED visits p < 0.001)). Regression analysis revealed that teaching hospitals were associated with higher odds of high CTA utilization (OR 1.88 for 2018, p < 0.05), while low-volume EDs and public hospitals showed the reverse (OR 0.39 in 2018, p < 0.05). CONCLUSIONS: We identified substantial increases in overall neuroimaging use in a national sample of non-admitted emergency department encounters between 2013 and 2018 with variability in utilization according to both patient and hospital properties. Further investigation into the appropriateness of this imaging is required to ensure that access to acute stroke treatment is balanced against the timing and cost of over-imaging.

On the merits and potential of advanced neuroimaging techniques in COVID-19: A scoping review.

Many Coronavirus Disease 2019 (COVID-19) patients are suffering from long-term neuropsychological sequelae. These patients may benefit from a better understanding of the underlying neuropathophysiological mechanisms and identification of potential biomarkers and treatment targets. Structural clinical neuroimaging techniques have limited ability to visualize subtle cerebral abnormalities and to investigate brain function. This scoping review assesses the merits and potential of advanced neuroimaging techniques in COVID-19 using literature including advanced neuroimaging or postmortem analyses in adult COVID-19 patients published from the start of the pandemic until December 2023. Findings were summarized according to distinct categories of reported cerebral abnormalities revealed by different imaging techniques. Although no unified COVID-19-specific pattern could be subtracted, a broad range of cerebral abnormalities were revealed by advanced neuroimaging (likely attributable to hypoxic, vascular, and inflammatory pathology), even in absence of structural clinical imaging findings. These abnormalities are validated by postmortem examinations. This scoping review emphasizes the added value of advanced neuroimaging compared to structural clinical imaging and highlights implications for brain functioning and long-term consequences in COVID-19.

Aortic valve Replacement compared to Transcatheter Implant and its relationship with COgnitive Impairment (ARTICO) evaluated with neuropsychological and advanced neuroimaging: a longitudinal cohort study.

BACKGROUND: Aortic stenosis is the most common valvulopathy in Western countries. The treatment of choice had been surgery aortic valve replacement (SAVR), but the improvement in endovascular approaches as transcatheter aortic valve implantation (TAVI), initially reserved for patients with very high surgical risk, has been extended to high and intermediate, and recently also to low-risk patients. Stroke and vascular cognitive impairment are the most important complications. It is not entirely clear which technique is best to avoid these complications as well as their impact. Our goal is to evaluate changes in cognitive performance in the early (1-month) and late (1-year) postoperative period in patients undergoing SAVR or TAVI, by extensive neuropsychological study (NRP) and advanced Magnetic Resonance Imaging (MRI). Specifically, to compare early and late cognitive changes after the intervention between both groups, the occurrence of stroke during follow-up and to compare the appearance of silent vascular lesions and changes in brain activity and functional connectivity with functional MRI during follow-up between both groups. METHODS/DESIGN: Prospective longitudinal cohort study. A non-selected representative sample of 80 subjects, 40 SAVR and 40 TAVI to obtain a final sample of 36 eligible subjects in each group, ranging from 70 to 85 years old, with indication for aortic replacement and intermediate or high surgical risk will be studied. At baseline, within one month before the treatment, all individuals will undergo an extensive NRP and advanced MRI study. These studies will also be performed 1-month and 1-year after treatment, to assess the appearance of new vascular lesions, as well as changes in cognitive performance with respect to baseline. DISCUSSION: This study aims to evaluate changes in cognitive performance as well as both clinical and silent vascular events occurring in the early (1-month) and late (1-year) periods after SAVR and TAVI. We will also analyze the correlation between neuropsychological and neuroimaging approaches in order to evaluate cognition. Therefore, it may provide high-quality data of cognitive changes and vascular events for both techniques, and be useful to tailor interventions to individual characteristics and ultimately aiding in decision-making. TRIAL REGISTRATION: This study is register in Clinicaltrials.gov (NCT05235529) on 11th February 2022.

Cluster headache pathophysiology: What we have learned from advanced neuroimaging.

BACKGROUND: Although remarkable progress has been achieved in understanding cluster headache (CH) pathophysiology, there are still several gaps about the mechanisms through which independent subcortical and cortical brain structures interact with each other. These gaps could be partially elucidated by structural and functional advanced neuroimaging investigations. OBJECTIVE: Although we are aware that substantial achievements have come from preclinical, neurophysiological, and biochemical experiments, the present narrative review aims to summarize the most significant findings from structural, microstructural, and functional neuroimaging investigations, as well as the consequent progresses in understanding CH pathophysiological mechanisms, to achieve a comprehensive and unifying model. RESULTS: Advanced neuroimaging techniques have contributed to overcoming the peripheral hypothesis that CH is of cavernous sinus pathology, in transitioning from the pure vascular hypothesis to a more comprehensive trigeminovascular model, and, above all, in clarifying the role of the hypothalamus and its connections in the genesis of CH. CONCLUSION: Altogether, neuroimaging findings strongly suggest that, beyond the theoretical model of the "pain matrix," the model of the "neurolimbic pain network" that is accepted in migraine research could also be extended to CH. Indeed, although the hypothalamus' role is undeniable, the genesis of CH attacks is complex and seems to not be just the result of a single "generator." Cortical-hypothalamic-brainstem functional interconnections that can switch between out-of-bout and in-bout periods, igniting the trigeminovascular system (probably by means of top-down mechanisms) and the consensual trigeminal autonomic reflexes, may represent the "neuronal background" of CH.

Making the Invisible Visible: Advanced Neuroimaging Techniques in Focal Epilepsy.

It has been a clinically important, long-standing challenge to accurately localize epileptogenic focus in drug-resistant focal epilepsy because more intensive intervention to the detected focus, including resection neurosurgery, can provide significant seizure reduction. In addition to neurophysiological examinations, neuroimaging plays a crucial role in the detection of focus by providing morphological and neuroanatomical information. On the other hand, epileptogenic lesions in the brain may sometimes show only subtle or even invisible abnormalities on conventional MRI sequences, and thus, efforts have been made for better visualization and improved detection of the focus lesions. Recent advance in neuroimaging has been attracting attention because of the potentials to better visualize the epileptogenic lesions as well as provide novel information about the pathophysiology of epilepsy. While the progress of newer neuroimaging techniques, including the non-Gaussian diffusion model and arterial spin labeling, could non-invasively detect decreased neurite parameters or hypoperfusion within the focus lesions, advances in analytic technology may also provide usefulness for both focus detection and understanding of epilepsy. There has been an increasing number of clinical and experimental applications of machine learning and network analysis in the field of epilepsy. This review article will shed light on recent advances in neuroimaging for focal epilepsy, including both technical progress of images and newer analytical methodologies and discuss about the potential usefulness in clinical practice.

Disconnectome of the migraine brain: a "connectopathy" model.

BACKGROUND: In the past decades a plethora of studies has been conducted to explore resting-state functional connectivity (RS-FC) of the brain networks in migraine with conflicting results probably due to the variability and susceptibility of signal fluctuations across the course of RS-FC scan. On the other hand, the structural substrates enabling the functional communications among the brain connectome, characterized by higher stability and reproducibility, have not been widely investigated in migraine by means of graph analysis approach. We hypothesize a rearrangement of the brain connectome with an increase of both strength and density of connections between cortical areas specifically involved in pain perception, processing and modulation in migraine patients. Moreover, such connectome rearrangement, inducing an imbalance between the competing parameters of network efficiency and segregation, may underpin a mismatch between energy resources and demand representing the neuronal correlate of the energetically dysfunctional migraine brain. METHODS: We investigated, using diffusion-weighted MRI imaging tractography-based graph analysis, the graph-topological indices of the brain "connectome", a set of grey matter regions (nodes) structurally connected by white matter paths (edges) in 94 patients with migraine without aura compared to 91 healthy controls. RESULTS: We observed in migraine patients compared to healthy controls: i) higher local and global network efficiency (p < 0.001) and ii) higher local and global clustering coefficient (p < 0.001). Moreover, we found changes in the hubs topology in migraine patients with: i) posterior cingulate cortex and inferior parietal lobule (encompassing the so-called neurolimbic-pain network) assuming the hub role and ii) fronto-orbital cortex, involved in emotional aspects, and visual areas, involved in migraine pathophysiology, losing the hub role. Finally, we found higher connection (edges) probability between cortical nodes involved in pain perception and modulation as well as in cognitive and affective attribution of pain experiences, in migraine patients when compared to healthy controls (p < 0.001). No correlations were found between imaging and clinical parameters of disease severity. CONCLUSION: The imbalance between the need of investing resources to promote network efficiency and the need of minimizing the metabolic cost of wiring probably represents the mechanism underlying migraine patients' susceptibility to triggers. Such changes in connectome topography suggest an intriguing pathophysiological model of migraine as brain "connectopathy".

Acute reperfusion therapies for acute ischemic stroke patients with unknown time of symptom onset or in extended time windows: an individualized approach.

Recent randomized controlled clinical trials (RCTs) have revolutionized acute ischemic stroke care by extending the use of intravenous thrombolysis and endovascular reperfusion therapies in time windows that have been originally considered futile or even unsafe. Both systemic and endovascular reperfusion therapies have been shown to improve outcome in patients with wake-up strokes or symptom onset beyond 4.5 h for intravenous thrombolysis and beyond 6 h for endovascular treatment; however, they require advanced neuroimaging to select stroke patients safely. Experts have proposed simpler imaging algorithms but high-quality data on safety and efficacy are currently missing. RCTs used diverse imaging and clinical inclusion criteria for patient selection during the dawn of this novel stroke treatment paradigm. After taking into consideration the dismal prognosis of nonrecanalized ischemic stroke patients and the substantial clinical benefit of reperfusion therapies in selected late presenters, we propose rescue reperfusion therapies for acute ischemic stroke patients not fulfilling all clinical and imaging inclusion criteria as an option in a subgroup of patients with clinical and radiological profiles suggesting low risk for complications, notably hemorrhagic transformation as well as local or remote parenchymal hemorrhage. Incorporating new data to treatment algorithms may seem perplexing to stroke physicians, since treatment and imaging capabilities of each stroke center may dictate diverse treatment pathways. This narrative review will summarize current data that will assist clinicians in the selection of those late presenters that will most likely benefit from acute reperfusion therapies. Different treatment algorithms are provided according to available neuroimaging and endovascular treatment capabilities.

Cost-Effectiveness Study of Initial Imaging Selection in Acute Ischemic Stroke Care.

PURPOSE: National guidelines recommend prompt identification of candidates for acute ischemic stroke (AIS) treatment, requiring timely neuroimaging with CT and/or MRI. CT is often preferred because of its widespread availability and rapid acquisition. Despite higher diagnostic accuracy of MRI, it commonly involves complex workflows that could potentially cause treatment time delays. The purpose of this study was to analyze the impact on outcomes of imaging utilization before treatment decisions at comprehensive stroke centers for patients presenting with suspected AIS in the anterior circulation with last-known-well-to-arrival time 0 to 24 hours. METHODS: A decision simulation model based on the American Heart Association's recommendations for AIS care pathways was developed from a health care perspective to compare initial imaging strategies: (1) stepwise-CT: noncontrast CT (NCCT) at the time of presentation, with CT angiography (CTA) ± CT perfusion (CTP) only in select patients (initial imaging to exclude hemorrhage and extensive ischemia) for mechanical thrombectomy (MT) evaluation; (2) stepwise-hybrid: NCCT at the time of presentation, with MR angiography (MRA) ± MR perfusion (MRP) only for MT evaluation; (3) stepwise-advanced: NCCT + CTA at presentation, with MR diffusion-weighted imaging (MR DWI) + MRP only for MT evaluation; (4) comprehensive-CT: NCCT + CTA + CTP at the time of presentation; and (5) comprehensive-MR: MR DWI + MRA + MRP at the time of presentation. Model parameters were defined using evidence-based data. Cost-effectiveness and sensitivity analyses were performed. RESULTS: The cost-effectiveness analyses revealed that comprehensive-CT and comprehensive-MR yield the highest lifetime quality-adjusted life-years (QALYs) (4.81 and 4.82, respectively). However, the incremental cost-effectiveness ratio of comprehensive-MR is $233,000/QALY compared with comprehensive-CT. Stepwise-CT, stepwise-hybrid, and stepwise-advanced strategies are dominated, yielding lower QALYs and higher costs compared with comprehensive-CT. CONCLUSIONS: Performing comprehensive-CT at presentation is the most cost-effective initial imaging strategy at comprehensive stroke centers.

Electroneurography and Advanced Neuroimaging Profile in Pediatric-onset Metachromatic Leukodystrophy.

CONTEXT: Metachromatic leukodystrophy (MLD) is a rare autosomal-recessive disorder characterized by demyelination of central and peripheral nervous system. There is scarcity of literature on the electrophysiological aspects of peripheral nerves and the advanced neuroimaging findings in MLD. AIM: The aim was to study the nerve conduction parameters and advanced neuroimaging findings in patients with MLD. MATERIALS AND METHODS: This study is a retrospective analysis conducted, between 2005 and 2016, of 12 patients who had biochemical, histopathological, or genetic confirmation of MLD and disease onset before 18 years of age. The clinical, electroneurography, and the advanced neuroimaging findings were reviewed and analyzed. STATISTICAL ANALYSIS: The data were presented as percentages or mean ± standard deviation as defined appropriate for qualitative and quantitative variables. RESULTS: Mean age of onset was 4.84 (±4.60) years and seven patients were males. Eight patients had juvenile MLD and four had late infantile MLD. Clinical presentation of psychomotor regression was more common in infantile MLD (75%), whereas gait difficulty (62.5%) and cognitive impairment (37.5%) were more frequent in juvenile MLD. Nerve conduction study (NCS) revealed diffuse demyelinating sensorimotor peripheral neuropathy in 9 (75%) patients. One patient had a rare presentation with conduction blocks in multiple nerves with contrast enhancement of cauda equina. Diffusion restriction involving periventricular and central white matter was seen in five patients and bilateral globus pallidi blooming was noted in three patients. CONCLUSION: This study highlights the utility of NCS and advanced magnetic resonance imaging sequences in the diagnosis of MLD.

Shedding light on migraine with aura: the clarifying role of advanced neuroimaging investigations.

Introduction: While migraine with aura is a complex neurological syndrome with a well-characterized clinical phenotype, its pathophysiology still has grey areas which could be partially clarified by microstructural and functional neuroimaging investigations. Areas covered: This article, summarizing the most significant findings from advanced neuroimaging studies, aims to achieve a unifying pathophysiological model of the migraine aura. A comprehensive review has been conducted of PubMed citations by entering the key word 'neuroimaging' combined with 'migraine with aura' AND/OR 'MRI.' Other keywords included 'grey matter' OR 'white matter', 'structural' OR 'functional'. Expert opinion: Converging evidence from advanced neuroimaging investigations underlined the critical role of the extrastriate visual cortex, and in particular the lingual gyrus, in the genesis of the aura phenomenon. However, the relationship between the aura and the headache phase of migraine attacks has not been completely clarified, to date, and underlying pathophysiological mechanisms need to be further elucidated.

Recent Insights in Migraine With Aura: A Narrative Review of Advanced Neuroimaging.

INTRODUCTION: Migraine is a complex neurological disorder characterized by severe headaches associated with a plethora of sensory hypersensitivity and neurovegetative symptoms. In about one-third of the cases, a set of fully reversible focal neurological symptoms, the aura, accompanies the headache. In the last decades, advanced neuroimaging investigations allowed identification of structural, microstructural, and functional abnormalities characterizing the brain of patients with migraine with aura (MwA). However, mechanisms underlying the aura phenomena are still a matter of debate. AIMS: This article reviews the most significant findings from advanced neuroimaging studies in patients with MwA both to provide a unifying physiopathological model of the aura phenomena and to clarify the potential impact of advanced neuroimaging investigation in the clinical field. METHODS: A comprehensive review of PubMed citations was conducted by entering the key words "magnetic resonance imaging" combined with "migraine" AND "aura." Other key words included "grey matter" OR "white matter," "structural" OR "functional." The only restriction was to English-language publications. The abstracts of all articles published between 1997 and 2018 meeting these criteria were reviewed, and the full texts were examined for relevance to the topic. CONCLUSION: Although several advanced neuroimaging studies have been conducted to investigate the neural correlates of aura phenomena, they have failed in identifying underlying pathophysiological mechanisms in their entirety. Nevertheless, functional and structural neuroimaging findings concerning the extrastriate visual cortex are characterized by a high level of reproducibility, so much so that they could be applied, in a not so far future, as diagnostic, prognostic, or therapeutic biomarkers for MwA.

Advanced Imaging in the Evaluation of Migraine Headaches.

The use of advanced imaging in routine diagnostic practice appears to provide only limited value in patients with migraine who have not experienced recent changes in headache characteristics or symptoms. However, advanced imaging may have potential for studying the biological manifestations and pathophysiology of migraine headaches. Migraine with aura appears to have characteristic spatiotemporal changes in structural anatomy, function, hemodynamics, metabolism, and biochemistry, whereas migraine without aura produces more subtle and complex changes. Large, controlled, multicenter imaging-based observational trials are needed to confirm the anecdotal evidence in the literature and test the scientific hypotheses thought to underscore migraine pathophysiology.

Advances in migraine neuroimaging and clinical utility: from the MRI to the bedside.

INTRODUCTION: In current migraine clinical practice, no specific diagnostic investigations are available and therefore the diagnosis is an eminently clinical process where instrumental examinations may have a part to exclude possible causes of secondary headaches. While migraine clinical phenotype has been widely characterized, migraine pathophysiology has still a gap that might be partly bridged by structural and functional neuroimaging investigations. Areas covered: This article aims to review the recent advances in functional neuroimaging, the consequent progress in the knowledge of migraine pathophysiology and their putative application and impact in the clinical setting. A comprehensive review was conducted of PubMed citations by entering the key word 'MRI' combined with 'migraine' AND/OR 'headache.' Other key words included 'gray matter' OR 'white matter,' 'structural' OR 'functional.' The only restriction was English-language publication. The abstracts of all articles meeting these criteria were reviewed, and full texts were examined for relevant references. Expert commentary: Advanced magnetic resonance imaging (MRI) techniques are tremendously improving our knowledge about brain abnormalities in migraine patients. However, advanced MRI could nowadays overcome the limits linked to the clinicians' judgment through the identification of objectively measurable neuroimaging findings (quantitative biomarkers) concerning the diagnosis, the prognosis and 'tailored' therapeutic-care pathways.

Is advanced neuroimaging for neuroradiologists? A systematic review of the scientific literature of the last decade.

INTRODUCTION: To evaluate if advanced neuroimaging research is mainly conducted by imaging specialists, we investigated the number of first authorships by radiologists and non-radiologist scientists in articles published in the field of advanced neuroimaging in the past 10 years. METHODS: Articles in the field of advanced neuroimaging identified in this retrospective bibliometric analysis were divided in four groups, depending on the imaging technique used. For all included studies, educational background of the first authors was recorded (based on available online curriculum vitae) and classified in subgroups, depending on their specialty. Finally, journal impact factors were recorded and comparatively assessed among subgroups as a metric of research quality. RESULTS: A total number of 3831 articles were included in the study. Radiologists accounted as first authors for only 12.8 % of these publications, while 56.9 % of first authors were researchers without a medical degree. Mean impact factor (IF) of journals with non-MD researchers as first authors was significantly higher than the MD subgroup (p < 10-20), while mean IF of journals with radiologists as first authors was significantly lower than articles authored by other MD specialists (p < 10-11). CONCLUSIONS: The majority of the studies in the field of advanced neuroimaging in the last decade is conducted by professional figures other than radiologists, who account for less than the 13 % of the publications. Furthermore, the mean IF value of radiologists-authored articles was the lowest among all subgroups. These results, taken together, should question the radiology community about its future role in the development of advanced neuroimaging.