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Intrinsic cerebrospinal fluid (CSF) dynamics in the brain have been extensively studied, particularly the egress sites of tagged intrinsic CSF in the meninges. Although spinal CSF recirculates within the central nervous system (CNS), we hypothesized that CSF outflows from the lumbar spinal canal. We aimed to visualize and semi-quantify the outflow using non-contrast MRI techniques. We utilized a 3 Tesla clinical MRI with a 16-channel spine coil, employing time-spatial labeling inversion (Time-SLIP) with tag-on and tag-off acquisitions, T2-weighted coronal 2D fluid-attenuated inversion recovery (FLAIR) and T2-weighted coronal 3D centric ky-kz single-shot FSE (cSSFSE). Images were acquired using time-spatial labeling inversion pulse (Time-SLIP) with tag-on and tag-off acquisitions with varying TI periods. Ten healthy volunteers with no known spinal diseases participated. Variations in tagged CSF outflow were observed across different thoracolumbar nerve root segments in all participants. We quantified CSF outflow at all lumbar levels and the psoas region. There was no significant difference among the ROIs for signal intensity. The tagged CSF outflow from the spinal canal is small but demonstrates egress to surrounding tissues. This finding may pave the way for exploring intrathecal drug delivery, understanding of CSF-related pathologies and its potential as a biomarker for peripheral neuropathy and radiculopathy.
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PURPOSE: Cerebrospinal fluid (CSF) clearance is essential for maintaining a healthy brain and cognition by removal of metabolic waste from the central nervous system. Physical exercise has been shown to improve human health; however, the effect of physical exercise on intrinsic CSF outflow in humans remains unexplored. The purpose of this study was to investigate intrinsic CSF outflow pathways and quantitative metrics of healthy individuals with active and sedentary lifestyles. In addition, the effect of exercise was investigated among the sedentary subjects before and after 3 weeks of physical activity. METHODS: This study was performed on 18 healthy adults with informed consent, using a clinical 3-Tesla MRI scanner. We classified participants into two groups based on reported time spent sitting per day (active group: < 7 hours sitting per day and sedentary group: ≥ 7 hours sitting per day). To elucidate the effect of exercise, sedentary individuals increased their activity to 3.5 hours for 3 weeks. RESULTS: We show that there are two intrinsic CSF egress pathways of the dura mater and lower parasagittal dura (PSD). The adults with an active lifestyle had greater intrinsic CSF outflow metrics than adults with a more sedentary lifestyle. However, after increased physical activity, the sedentary group showed improved CSF outflow metrics. This improvement was particularly notable at the lower PSD, where outflow metrics were highest among the active group. CONCLUSION: Our findings describe the relationship between physical activity and intrinsic CSF outflow and show a potential selective outflow pathway with increasing physical activity in the lower PSD pathway, potentially from the perivascular space or cortical venous subpial space.
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Encéfalo , Exercício Físico , Adulto , Humanos , Encéfalo/fisiologia , Imageamento por Ressonância Magnética , Dura-MáterRESUMO
PURPOSE: Fatty acid composition of the orbit makes it challenging to achieve complete fat suppression during orbit MR imaging. Implementation of a fat suppression technique capable of suppressing signals from saturated (aliphatic) and unsaturated (olefinic or protons at double-bonded carbon sites) fat would improve the visualization of an optical nerve. Furthermore, the ability to semi-quantify the fractions of aliphatic and olefinic fat may potentially provide valuable information in assessing orbit pathology. METHODS: A phantom study was conducted on various oil samples on a clinical 3 Tesla scanner. The imaging protocol included three 2D fast spin echo (FSE) sequences: in-phase, polarity-altered spectral and spatial selective acquisition (PASTA), and a combination of PASTA with opposed phase in olefinic and aliphatic chemical shift. The results were validated against high-resolution 11.7T NMR and compared with images acquired with spectral attenuated inversion recovery (SPAIR) and chemical shift selective (CHESS) fat suppression techniques. In-vivo data were acquired on eight healthy subjects and were compared with the prior histological studies. RESULTS: PASTA with opposed phase achieved complete suppression of fat signals in the orbits and provided images of well-delineated optical nerves and muscles in all subjects. The olefinic fat fraction in the olive, walnut, and fish oil phantoms at 3T was found to be 5.0%, 11.2%, and 12.8%, respectively, whereas 11.7T NMR provides the following olefinic fat fractions: 6.0% for olive, 11.5% for walnut, and 12.6% for fish oils. For the in-vivo study, on average, olefinic fat accounted for 9.9% ± 3.8% of total fat while the aliphatic fat fraction was 90.1% ± 3.8%, in the normal orbits. CONCLUSION: We have introduced a new fat suppression technique using PASTA with opposed phase and applied it to human orbits. The purposed method achieves an excellent orbital fat suppression and the quantification of aliphatic and olefinic fat signals.
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Alcenos , Órbita , Humanos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Imagens de Fantasmas , Tecido Adiposo/diagnóstico por imagemRESUMO
PURPOSE: Clearance of cerebrospinal fluid (CSF) is important for the removal of toxins from the brain, with implications for neurodegenerative diseases. Imaging evaluation of CSF outflow in humans has been limited, relying on venous or invasive intrathecal injections of contrast agents. The objective of this study was to introduce a novel spin-labeling MRI technique to detect and quantify the movement of endogenously tagged CSF, and then apply it to evaluate CSF outflow in normal humans of varying ages. METHODS: This study was performed on a clinical 3-Tesla MRI scanner in 16 healthy subjects with an age range of 19-71 years with informed consent. Our spin-labeling MRI technique applies a tag pulse on the brain hemisphere, and images the outflow of the tagged CSF into the superior sagittal sinus (SSS). We obtained 3D images in real time, which was analyzed to determine tagged-signal changes in different regions of the meninges involved in CSF outflow. Additionally, the signal changes over time were fit to a signal curve to determine quantitative flow metrics. These were correlated against subject age to determine aging effects. RESULTS: We observed the signal of the tagged CSF moving from the dura mater and parasagittal dura, and finally draining into the SSS. In addition, we observed a possibility of another pathway which is seen in some young subjects. Furthermore, quantitative CSF outflow metrics were shown to decrease significantly with age. CONCLUSION: We demonstrate a novel non-invasive MRI technique identifying two intrinsic CSF clearance pathways, and observe an age-related decline of CSF flow metrics in healthy subjects. Our work provides a new opportunity to better understand the relationships of these CSF clearance pathways during the aging process, which may ultimately provide insight into the age-related prevalence of neurodegenerative diseases.
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OBJECTIVE: Predict hearing preservation after middle cranial fossa approach for vestibular schwannomas. STUDY DESIGN: Application of machine learning algorithms, including classification and regression trees and random forest models to observational data. SETTING: Single-tertiary referral center. PARTICIPANTS: Patients (n = 144) with a previously untreated sporadic vestibular schwannoma who underwent microsurgical resection by middle cranial fossa approach between November 2017 and November 2021. INTERVENTIONS: Middle cranial fossa approach. MAIN OUTCOME AND MEASURES: Hearing preservation, defined by postoperative word recognition score of 50% or greater and pure tone average below 50 dB HL or less than 10% reduction in word recognition score. Model performance was evaluated with classification accuracy in an independent validation sample. Variable importance for the random forest model is reported according to entropy, a measure of mean decrease in model accuracy incurred by excluding each variable from the model. RESULTS: Hearing preservation was achieved in 60% of patients (86 of 144) overall. The classification and regression tree model identified preoperative pure tone average with a cut point of 30 dB HL, and more posterior tumor position to be the most important prognostic features for hearing preservation. Model accuracy was 0.68. The random forest model demonstrated perfect accuracy (1). Baseline pure tone average, word recognition score, and anteroposterior tumor position were among the most influential features for hearing preservation prediction. CONCLUSION: Machine learning algorithms have the potential for accurate prediction of hearing preservation rates after middle fossa approach for vestibular schwannomas at a single institution. These models have the capacity for continued refinement with ongoing addition of data.
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Neuroma Acústico , Fossa Craniana Média/cirurgia , Audição , Humanos , Aprendizado de Máquina , Neuroma Acústico/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Objectives Dispersion of bone dust in the posterior fossa during retrosigmoid craniectomy for vestibular schwannoma (VS) resection could be a source of meningeal irritation and lead to development of persistent postoperative headaches (POH). We aim to determine risk factors, including whether the presence of bone spicules that influence POH after retrosigmoid VS resection. Design Present study is a retrospective case series. Setting The study was conducted at a tertiary skull-base referral center. Participants Adult patients undergoing VS resection via a retrosigmoid approach between November 2017 and February 2020 were included for this study. Main Outcome Measures Development of POH lasting ≥ 3 months is the primary outcome of this study. Results Of 64 patients undergoing surgery, 49 had complete data (mean age, 49 years; 53% female). Mean follow-up time was 2.4 years. At latest follow up, 16 (33%) had no headaches, 14 (29%) experienced headaches lasting <3 months, 19 (39%) reported POH lasting ≥3 months. Twenty-seven (55%) patients had posterior fossa bone spicules detectable on postoperative computed tomography (CT). Age, gender, body mass index, length of stay, tumor diameter, size of craniectomy, the presence of bone spicules, or the amount of posterior petrous temporal bone removed from drilling did not differ significantly between patients with POH and those without. On multivariate logistic regression, patients with POH were less likely to have preoperative brainstem compression by the tumor (odds ratio [OR] = 0.21, p = 0.028) and more likely to have higher opioid requirements during hospitalization (OR = 1.023, p = 0.045). Conclusion The presence of bone spicules in the posterior fossa on postoperative CT did not contribute to headaches following retrosigmoid craniectomy approach for VS resection.
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Síndrome Pós-Laminectomia/diagnóstico por imagem , Laminectomia/efeitos adversos , Radiculopatia/diagnóstico por imagem , Aderências Teciduais/complicações , Aderências Teciduais/diagnóstico por imagem , Adulto , Síndrome Pós-Laminectomia/etiologia , Síndrome Pós-Laminectomia/patologia , Feminino , Humanos , Região Lombossacral , Imageamento por Ressonância Magnética , Radiculopatia/etiologia , Radiculopatia/patologia , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Aderências Teciduais/patologiaRESUMO
Nontraumatic neck pain is a leading cause of disability, with nearly 50% of individuals experiencing ongoing or recurrent symptoms. Radiographs are appropriate as initial imaging for cervical or neck pain in the absence of "red flag" symptoms or if there are unchanging chronic symptoms; however, spondylotic changes are commonly identified and may result in both false-positive and false-negative findings. Noncontrast CT can be complementary to radiographs for evaluation of new or changing symptoms in the setting of prior cervical spine surgery or in the assessment of extent of ossification in the posterior longitudinal ligament. Noncontrast MRI is usually appropriate for assessment of new or increasing radiculopathy due to improved nerve root definition. MRI without and with contrast is usually appropriate in patients with new or increasing cervical or neck pain or radiculopathy in the setting of suspected infection or known malignancy. Imaging may be appropriate; however, it is not always indicated for evaluation of cervicogenic headache without neurologic deficit. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
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Cervicalgia/diagnóstico por imagem , Radiculopatia/diagnóstico por imagem , Meios de Contraste , Diagnóstico Diferencial , Medicina Baseada em Evidências , Humanos , Sociedades Médicas , Estados UnidosRESUMO
BACKGROUND AND IMPORTANCE: Flow diversion for the treatment of aneurysm-induced hemifacial spasm (HFS) has not been previously described. CLINICAL PRESENTATION: The authors present the case of a 60-yr-old woman who presented with 1 yr of progressive left HFS secondary to a vertebral artery aneurysm compressing the root entry zone of cranial nerve VII. The patient's aneurysm was successfully treated with a flow diverting stent. CONCLUSION: In the immediate postoperative period, the patient had near complete resolution of her HFS symptoms. At her 6-mo follow-up the patient had no angiographic filling of the aneurysm and her HFS symptoms had completely resolved.
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Embolização Terapêutica , Procedimentos Endovasculares , Espasmo Hemifacial/cirurgia , Aneurisma Intracraniano/complicações , Artéria Vertebral/fisiopatologia , Feminino , Espasmo Hemifacial/etiologia , Humanos , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Resultado do TratamentoRESUMO
BACKGROUND: While data from several studies over the last decade has demonstrated that introduction of immunologic checkpoint blockage therapy with anti-CTLA-4/PD-1 drugs leads to improved survival in metastatic melanoma patients, relatively little is known about brain-specific therapeutic response and adverse events in the context of immunotherapeutic treatment of intracranial disease. Here we report two independent cases of new intracranial metastases presenting after initiation of combined checkpoint blockade Ipilimumab and Nivolumab for recurrent metastatic melanoma in the context of positive systemic disease response. CASE PRESENTATION: Case #1: A 43-year-old Caucasian male with Stage III melanoma of the left knee had subsequent nodal, hepatic and osseous metastases and was started on ipilimumab/nivolumab. He developed an intractable headache one week later. MRI revealed new enhancing and hemorrhagic brain metastases. After 6 weeks of immunotherapy, there was interval hemorrhage of a dominant intracranial lesion but substantial improvement in systemic metastatic disease. Durable, near complete intracranial and systemic response was achieved after completion of both induction and maintenance immunotherapy. Case #2: A 58-year old Caucasian woman with stage II melanoma of the right index finger developed cutaneous, pulmonary and hepatic metastases within 4 months of adjuvant radiation. Although combined checkpoint blockade resulted in improvement in both cutaneous and systemic disease, brain MR performed for eye discomfort demonstrated new enhancing and hemorrhagic brain metastases. Serial MR imaging five months later revealed only a solitary focus of brain enhancement with continued improved systemic disease. CONCLUSIONS: These cases raise the question of whether the initial immune activation and modulation of the blood brain barrier by Ipilimumab/Nivolumab somehow "unmasks" previously clinically silent metastatic disease, rather than representing new or progressive metastatic disease. An overview of currently available literature discussing the role of immune checkpoint blockade in the treatment of intracranial metastatic melanoma will be provided, as well as discussion highlighting the need for future work elucidating the response of brain metastases to anti-CTLA/PD-1 drugs and documentation of brain-specific adverse events.
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Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/secundário , Melanoma/secundário , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Cutâneas/patologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/tratamento farmacológico , Feminino , Humanos , Ipilimumab/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Melanoma/diagnóstico , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Nivolumabe/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Resultado do TratamentoRESUMO
Synapse elimination at the developing neuromuscular junction (NMJ) sculpts motor circuits, and synapse loss at the aging NMJ drives motor impairments that are a major cause of loss of independence in the elderly. Here we provide evidence that at the NMJ, both developmental synapse elimination and aging-related synapse loss are promoted by specific immune proteins, members of the major histocompatibility complex class I (MHCI). MHCI is expressed at the developing NMJ, and three different methods of reducing MHCI function all disrupt synapse elimination during the second postnatal week, leaving some muscle fibers multiply-innervated, despite otherwise outwardly normal synapse formation and maturation. Conversely, overexpressing MHCI modestly accelerates developmental synapse elimination. MHCI levels at the NMJ rise with aging, and reducing MHCI levels ameliorates muscle denervation in aged mice. These findings identify an unexpected role for MHCI in the elimination of neuromuscular synapses during development, and indicate that reducing MHCI levels can preserve youthful innervation of aging muscle.