Methylene blue modulates functional connectivity in the human brain.

Methylene blue USP (MB) is a FDA-grandfathered drug used in clinics to treat methemoglobinemia, carbon monoxide poisoning and cyanide poisoning that has been shown to increase fMRI evoked blood oxygenation level dependent (BOLD) response in rodents. Low dose MB also has memory enhancing effect in rodents and humans. However, the neural correlates of the effects of MB in the human brain are unknown. We tested the hypothesis that a single low oral dose of MB modulates the functional connectivity of neural networks in healthy adults. Task-based and task-free fMRI were performed before and one hour after MB or placebo administration utilizing a randomized, double-blinded, placebo-controlled design. MB administration was associated with a reduction in cerebral blood flow in a task-related network during a visuomotor task, and with stronger resting-state functional connectivity in multiple regions linking perception and memory functions. These findings demonstrate for the first time that low-dose MB can modulate task-related and resting-state neural networks in the human brain. These neuroimaging findings support further investigations in healthy and disease populations.

Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain.

Purpose To investigate the sustained-attention and memory-enhancing neural correlates of the oral administration of methylene blue in the healthy human brain. Materials and Methods The institutional review board approved this prospective, HIPAA-compliant, randomized, double-blinded, placebo-controlled clinical trial, and all patients provided informed consent. Twenty-six subjects (age range, 22-62 years) were enrolled. Functional magnetic resonance (MR) imaging was performed with a psychomotor vigilance task (sustained attention) and delayed match-to-sample tasks (short-term memory) before and 1 hour after administration of low-dose methylene blue or a placebo. Cerebrovascular reactivity effects were also measured with the carbon dioxide challenge, in which a 2 × 2 repeated-measures analysis of variance was performed with a drug (methylene blue vs placebo) and time (before vs after administration of the drug) as factors to assess drug × time between group interactions. Multiple comparison correction was applied, with cluster-corrected P < .05 indicating a significant difference. Results Administration of methylene blue increased response in the bilateral insular cortex during a psychomotor vigilance task (Z = 2.9-3.4, P = .01-.008) and functional MR imaging response during a short-term memory task involving the prefrontal, parietal, and occipital cortex (Z = 2.9-4.2, P = .03-.0003). Methylene blue was also associated with a 7% increase in correct responses during memory retrieval (P = .01). Conclusion Low-dose methylene blue can increase functional MR imaging activity during sustained attention and short-term memory tasks and enhance memory retrieval. © RSNA, 2016 Online supplemental material is available for this article.

Imaging of Orbital Trauma and Emergent Non-traumatic Conditions.

Diagnostic imaging has become critical in the care of patients suffering from traumatic or nontraumatic emergent orbital conditions. Multidetector computed tomography (MDCT) has become the standard imaging modality for assessing orbital trauma because of its accurate assessment of orbital skeletal and soft tissues injuries. Contrast-enhanced MR imaging is the first-line examination in the assessment of nontraumatic orbital conditions given its excellent evaluation of the orbital soft tissues. Conventional angiography is necessary in some vascular orbital complications and allows for endovascular treatment. This article discusses the spectrum of orbital pathology encountered in the imaging of orbital trauma and nontraumatic orbital emergencies.

Safety and Efficacy of Gadobutrol for Contrast-enhanced Magnetic Resonance Imaging of the Central Nervous System: Results from a Multicenter, Double-blind, Randomized, Comparator Study.

PURPOSE: Contrast-enhanced magnetic resonance imaging (MRI) of the central nervous system (CNS) with gadolinium-based contrast agents (GBCAs) is standard of care for CNS imaging and diagnosis because of the visualization of lesions that cause blood-brain barrier breakdown. Gadobutrol is a macrocyclic GBCA with high concentration and high relaxivity. The objective of this study was to compare the safety and efficacy of gadobutrol 1.0 M vs unenhanced imaging and vs the approved macrocyclic agent gadoteridol 0.5 M at a dose of 0.1 mmol/kg bodyweight. MATERIALS AND METHODS: Prospective, multicenter, double-blind, crossover trial in patients who underwent unenhanced MRI followed by enhanced imaging with gadobutrol or gadoteridol. Three blinded readers assessed the magnetic resonance images. The primary efficacy variables included number of lesions detected, degree of lesion contrast-enhancement, lesion border delineation, and lesion internal morphology. RESULTS: Of the 402 treated patients, 390 patients received study drugs. Lesion contrast-enhancement, lesion border delineation, and lesion internal morphology were superior for combined unenhanced/gadobutrol-enhanced imaging vs unenhanced imaging (P < 0.0001 for all). Compared with gadoteridol, gadobutrol was non-inferior for all primary variables and superior for lesion contrast-enhancement, as well as sensitivity and accuracy for detection of malignant disease. The percentage of patients with at least one drug-related adverse event was similar for gadobutrol (10.0%) and gadoteridol (9.7%). CONCLUSION: Gadobutrol is an effective and well-tolerated macrocyclic contrast agent for MRI of the CNS. Gadobutrol demonstrates greater contrast-enhancement and improved sensitivity and accuracy for detection of malignant disease than gadoteridol, likely because of its higher relaxivity.

Phase 3 efficacy and safety trial of gadobutrol, a 1.0 molar macrocyclic MR imaging contrast agent, in patients referred for contrast-enhanced MR imaging of the central nervous system.

PURPOSE: Gadobutrol is a 1.0 M macrocyclic magnetic resonance imaging (MRI) contrast agent. A study was performed to evaluate the efficacy and safety of gadobutrol-enhanced versus unenhanced imaging for central nervous system (CNS) lesion visualization and detection. MATERIALS AND METHODS: An international, multicenter, open-label, Phase III clinical trial. Patients underwent unenhanced and gadobutrol 1.0 M-enhanced (0.1 mmol/kg BW) MR imaging using a standardized protocol. Unenhanced and combined unenhanced/gadobutrol-enhanced images were scored by three independent, blinded readers for degree of lesion enhancement, border delineation, internal morphology, and total number of lesions detected (primary efficacy variables). Exact match of the MR diagnoses with the final clinical diagnosis, detection of malignant CNS lesions, and confidence in diagnosis were secondary efficacy variables. RESULTS: Of 343 enrolled patients, 321 were evaluated for efficacy. All primary efficacy endpoints were met: superiority was demonstrated for gadobutrol-enhanced versus unenhanced MR images (P < 0.0001 in all cases) for lesion enhancement, border delineation, and internal morphology. Noninferiority was met for mean number of lesions detected. There were improvements in the sensitivity of malignant lesion detection, without a loss in specificity, exact-match diagnostic accuracy, and reader confidence. Treatment-related adverse events were reported in 4.1% (n = 14); all were nonserious. CONCLUSION: Gadobutrol 1.0M is an effective and well-tolerated contrast agent for CNS MRI.

Choroidal blood flow decreases with age: an MRI study.

PURPOSE: To verify that a visual fixation protocol with cued eye blinks achieves sufficient stability for magnetic resonance imaging (MRI) blood-flow measurements and to determine if choroidal blood flow (ChBF) changes with age in humans. METHODS: The visual fixation stability achievable during an MRI scan was measured in five normal subjects using an eye-tracking camera outside the MRI scanner. Subjects were instructed to blink immediately after recorded MRI sound cues but to otherwise maintain stable visual fixation on a small target. Using this fixation protocol, ChBF was measured with MRI using a 3 Tesla clinical scanner in 17 normal subjects (24-68 years old). Arterial and intraocular pressures (IOP) were measured to calculate perfusion pressure in the same subjects. RESULTS: The mean temporal fluctuations (standard deviation) of the horizontal and vertical displacements were 29 ± 9 µm and 38 ± 11 µm within individual fixation periods, and 50 ± 34 µm and 48 ± 19 µm across different fixation periods. The absolute displacements were 67 ± 31 µm and 81 ± 26 µm. ChBF was negatively correlated with age (R = -0.7, p = 0.003), declining 2.7 ml/100 ml/min per year. There were no significant correlations between ChBF versus perfusion pressure, arterial pressure, or IOP. There were also no significant correlations between age versus perfusion pressure, arterial pressure, or IOP. Multiple regression analysis indicated that age was the only measured independent variable that was significantly correlated with ChBF (p = 0.03). CONCLUSIONS: The visual fixation protocol with cued eye blinks was effective in achieving sufficient stability for MRI measurements. ChBF had a significant negative correlation with age.

Use of contrast media in neuroimaging.

Since their introduction, gadolinium-based contrast media are routinely used in most CNS MR imaging indications. Due to their paramagnetic effect, they significantly shorten the T1 relaxation times of the tissue and are therefore applied to improve the sensitivity and specificity of CNS diseases and to allow a better treatment decision, planning, and follow-up. More recently, contrast media have also been used to allow the measurement of tissue perfusion and to follow the time course of enhancement in dynamic contrast-enhanced imaging studies or dynamic MRA studies. With the presence of the BBB, contrast media does not leak into the tissue. Only vascular structures and areas of the brain that have no BBB(choroid plexus, pineal and anterior lobe of pituitary gland) physiologically enhance after contrast injection. The mechanisms of tissue enhancement in the brain are related to a higher vascularity of the pathology or a disruption of the BBB.Tissue enhancement is, besides the degree of BBB disruption, further dependent on the applied magnetic field strength, with higher field providing a better enhancement and the applied dose of contrast media.

Contrast-enhanced MR imaging in neuroimaging.

MR imaging without and with gadolinium-based contrast agents (GBCAs) is an important imaging tool for defining normal anatomy and characteristics of lesions. GBCAs have been used in contrast-enhanced MR imaging in defining and characterizing lesions of the central nervous system for more than 20 years. The combination of unenhanced and GBCA-enhanced MR imaging is the clinical gold standard for the noninvasive detection and delineation of most intracranial and spinal lesions. MR imaging has a high predictive value that rules out neoplasm and most inflammatory and demyelinating processes of the central nervous system.

Penetrating neck injuries: helical CT angiography for initial evaluation.

PURPOSE: To report an experience with helical computed tomographic (CT) angiography as the initial procedure to rule out arterial lesions caused by penetrating neck injuries. MATERIALS AND METHODS: During 27 months, 175 patients were referred for helical CT angiography of the neck because of clinical suspicion of arterial injuries. The protocol included a 100-mL bolus of nonionic contrast material injected at 4.5 mL/sec, with 11-second scanning delay, 3-mm collimation, and pitch of 1.3-2.0. CT images were interpreted prospectively by the emergency radiologist, and two radiologists retrospectively interpreted studies with consensus. Outcome was determined with examination of patients and their charts. The sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: Studies in two patients were considered inadequate for diagnosis; these patients were referred for conventional arteriography and had normal findings. In 27 patients (15.6%), arterial lesions were detected. One patient had two arterial injuries. Lesions demonstrated with helical CT angiography were arterial occlusion (n = 14), pseudoaneurysm (n = 8), pseudoaneurysm and arteriovenous fistulae (n = 4), and partial thrombosis (n = 2). The remaining 146 patients had normal arteries. On the basis of these findings, patients were treated with surgery (n = 21), endovascular intervention (n = 7), and observation alone (n = 146). CONCLUSION: Results indicate that helical CT angiography can be used as the initial method for evaluation in patients with possible arterial injuries of the neck.

Statistical analyses of structural magnetic resonance imaging of the head of the caudate nucleus in Colombian children with attention-deficit hyperactivity disorder.

Magnetic resonance imaging (MRI) studies of the caudate nucleus have reported reversal asymmetry and alterations of its size, suggesting a striate cortical disorder related to attention-deficit hyperactivity disorder (ADHD). The objective was to evaluate whether alterations of the asymmetry and size of the caudate nucleus head exist in a sample of well-controlled 7- to 11-year-old Colombian children, with different types of ADHD. Two groups of cases-ADHD of the combined type and ADHD of the inattentive type-and one control group, were selected. Multiple methods for assessing ADHD (rating scales, psychologic.interview, neurologic history and examination, and neuropsychologic evaluation) were used to confirm the diagnoses. Participants with a history of language disorder, learning disabilities, depression, and other major neurologic and psychiatric conditions were excluded. Finally all groups had 15 children, matched by sex (7 male, 8 female), age, socioeconomic status, and grade. Height, weight, head circumference, and encephalic index were statistically controlled. Three T1-weighted volumetric (three-dimensional) MRI slides of the caudate nucleus head were obtained with a 1.5-Tesla Gyroscan apparatus. The control group had a significantly higher Wechsler Full-Scale IQ than the groups with ADHD of the combined type and ADHD of the inattentive type (P < .001). Volumes from the left caudate nucleus head were significantly larger than volumes from the right in all groups (P < .001). There were no group differences when volumes were compared between groups. All of the groups had left caudate nucleus head volumes significantly higher than right, although there were no between-group differences. The results in relation to previous studies are discussed.