Low-Field (64mT) Portable MRI for Rapid Point-of-Care Diagnosis of DIS in Patients Presenting with Optic Neuritis.

BACKGROUND AND PURPOSE: Low-field 64mT portable brain MRI (pMRI) has recently shown diagnostic promise for MS. This study aimed to evaluate the utility of pMRI in assessing dissemination in space (DIS) in patients presenting with optic neuritis and determine whether deploying pMRI in the MS clinic can shorten the time from symptom onset to MRI. MATERIALS AND METHODS: Newly diagnosed optic neuritis patients referred to a tertiary academic MS center from July 2022 to January 2024 underwent both point-of-care pMRI and subsequent conventional 3T MRI (cMRI). Images were evaluated for periventricular (PV), juxtacortical (JC) and infratentorial (IT) lesions. DIS was determined on brain MRI per 2017 McDonald criteria. Test characteristics were computed using cMRI as the reference. Interrater and intermodality agreement between pMRI and cMRI were evaluated using Cohen's kappa. Time from symptom onset to pMRI and cMRI during the study period was compared to the preceding 1.5 years before pMRI implementation using Kruskal-Wallis with post-hoc Dunn's tests. RESULTS: Twenty patients (median age: 32.5 [IQR, 28-40]; 80% females) were included, of whom 9 (45%) and 5 (25%) had DIS on cMRI and pMRI, respectively. Median time interval between pMRI and cMRI was 7 days (IQR, 3.5-12.5). Interrater agreement was very good for PV (95%, κ=0.89), and good for JC and IT lesions (90%, κ=0.69 for both). Intermodality agreement was good for PV (90%, κ=0.80) and JC (85%, κ=0.63), and moderate for IT lesions (75%, κ=0.42) and DIS (80%, κ=0.58). pMRI had a sensitivity of 56% and specificity of 100% for DIS.The median time from symptom onset to pMRI was significantly shorter (8.5 days [IQR 7-12]) compared to the interval to cMRI before pMRI deployment (21 days [IQR 8-49], n=50) and after pMRI deployment (15 days [IQR 12-29], n=30) (both p<0.01). Time from symptom onset to cMRI in those periods was not significantly different (p=0.29). CONCLUSIONS: In optic neuritis patients, pMRI exhibited moderate concordance, moderate sensitivity and high specificity for DIS compared to cMRI. Its integration into the MS clinic reduced the time from symptom onset to MRI. Further studies are warranted to evaluate the role of pMRI in expediting early MS diagnosis and as an imaging tool in resource-limited settings. ABBREVIATIONS: pMRI = portable MRI; cMRI = conventional MRI; pwMS = patients with MS; PV = periventricular; JC= juxtacortical; IT = infratentorial; DIS = dissemination in space.

Nonaneurysmal perimesencephalic subarachnoid hemorrhage on noncontrast head CT: An accuracy, inter-rater, and intra-rater reliability study.

BACKGROUND AND PURPOSE: To evaluate the reliability and accuracy of nonaneurysmal perimesencephalic subarachnoid hemorrhage (NAPSAH) on Noncontrast Head CT (NCCT) between numerous raters. MATERIALS AND METHODS: 45 NCCT of adult patients with SAH who also had a catheter angiography (CA) were independently evaluated by 48 diverse raters; 45 raters performed a second assessment one month later. For each case, raters were asked: 1) whether they judged the bleeding pattern to be perimesencephalic; 2) whether there was blood anterior to brainstem; 3) complete filling of the anterior interhemispheric fissure (AIF); 4) extension to the lateral part of the sylvian fissure (LSF); 5) frank intraventricular hemorrhage; 6) whether in the hypothetical presence of a negative CT angiogram they would still recommend CA. An automatic NAPSAH diagnosis was also generated by combining responses to questions 2-5. Reliability was estimated using Gwet's AC1 (κG), and the relationship between the NCCT diagnosis of NAPSAH and the recommendation to perform CA using Cramer's V test. Multi-rater accuracy of NCCT in predicting negative CA was explored. RESULTS: Inter-rater reliability for the presence of NAPSAH was moderate (κG = 0.58; 95%CI: 0.47, 0.69), but improved to substantial when automatically generated (κG = 0.70; 95%CI: 0.59, 0.81). The most reliable criteria were the absence of AIF filling (κG = 0.79) and extension to LSF (κG = 0.79). Mean intra-rater reliability was substantial (κG = 0.65). NAPSAH weakly correlated with CA decision (V = 0.50). Mean sensitivity and specificity were 58% (95%CI: 44%, 71%) and 83 % (95%CI: 72 %, 94%), respectively. CONCLUSION: NAPSAH remains a diagnosis of exclusion. The NCCT diagnosis was moderately reliable and its impact on clinical decisions modest.

Delayed Gadolinium Leakage in Ocular Structures on Brain MR Imaging: Prevalence and Associated Factors.

BACKGROUND AND PURPOSE: Gadolinium leakage in ocular structures (GLOS) is characterized by hyperintense signal in the chambers of the eye on FLAIR and has been reported in association with blood-ocular barrier breakdown in patients with ischemic strokes. The underlying mechanism of GLOS remains poorly understood; however, some studies suggest it may be part of a physiologic excretion pathway of gadolinium. This study aimed to determine the prevalence of GLOS in an unselected patient population. MATERIALS AND METHODS: A retrospective analysis was conducted on 439 patients who underwent brain MR imaging within 7 days of receiving a gadolinium-based contrast agent injection for a prior MR imaging study. Clinical, imaging, and laboratory data were collected. Descriptive and logistic regression analyses were performed. RESULTS: GLOS was observed in 26 of 439 patients (6%). The occurrence of GLOS varied with time, with 3 (12%), 14 (54%), 8 (31%), and 1 (4%) patient showing GLOS within 24, 25-72, 73-120, and >120 hours after gadolinium-based contrast agent injection, respectively. Patients with GLOS were older (median age: 72 versus 55 years, P = .001) and had higher median serum creatinine levels (73 versus 64 µmol/L, P = .005) and a lower median estimated glomerular filtration rate (84 versus 101 mL/min/1.73 m2, P < .001). A shorter median time interval between gadolinium-based contrast agent injection and the index brain MR imaging was observed in the group positive for GLOS (62 versus 91 hours, P = .003). Multivariable regression analysis identified the estimated glomerular filtration rate (OR = 0.970; 95% CI, 0.049-0.992; P = .008) and time interval since gadolinium-based contrast agent injection (OR = 0.987; 95% CI, 0.977-0.997; P = .012) as independent factors associated with GLOS. CONCLUSIONS: GLOS was observed in only a small percentage of patients receiving gadolinium-based contrast agent within 7 days before brain MR imaging. This phenomenon was noted in patients with normal findings on brain MR imaging and those with various CNS pathologies, and it was associated with lower estimated glomerular filtration rates and shorter time intervals after gadolinium-based contrast agent injection. While GLOS may be a physiologic gadolinium-based contrast agent excretion pathway, the presence of ocular disease was not formally evaluated in the included population. Awareness of GLOS is nonetheless useful for appropriate radiologic interpretation.

Potential application of ultra-low field portable MRI in the ICU to improve CT and MRI access in Canadian hospitals: a multi-center retrospective analysis.

Background: To highlight the value of Portable MRI in ICU and to recommend use case scenarios for portable MRI in ICU patients that may increase capacity for fixed CT and MRI units. Urgent neuroimaging is commonly required in ICU. Typically, ICU patients are transported to Radiology for assessment in fixed CT and MRI units. Portable MRI use in Canadian ICU settings offers the potential advantages of reduced transport risk, earlier diagnosis, improved triaging, as well as the ability to perform frequent re-imaging at the bedside. This frees up time on fixed CT and MRI units, leading to enhanced capacity to perform CT and MRI on other patients. Portable MRI use case scenarios in Canadian institutions have not been established and potential beneficial effect on wait times has not been analyzed. Methods: A retrospective semi-quantitative descriptive analysis was performed using all ICU neuroimaging requisitions (CT and MRI) over a 12-month period between January and December 2021, at Kingston Health Sciences Centre, Queen's University (Kingston, Ontario) and St. Michael's Hospital, Unity Health, University of Toronto (Toronto, Ontario). Indications for portable MRI in ICU patients were established. The number of ICU patients who could potentially undergo portable MRI was determined. Fixed CT and MRI scan times saved were calculated. Results: In ICU patients, portable MRI could potentially replace fixed CT in 21% and fixed MRI in 26.5% of cases. This equates to annual capacity increase of 1,676 additional patients being able to undergo fixed CT scans and 324 additional patients being able to undergo fixed MRI. Conclusion: Implementation of portable MRI in the ICU for select neurological indications can have a significant positive impact on CT and MRI wait times in Canadian hospitals.

Chemical genetic identification of GAK substrates reveals its role in regulating Na+/K+-ATPase.

Cyclin G-associated kinase (GAK) is a ubiquitous serine/threonine kinase that facilitates clathrin uncoating during vesicle trafficking. GAK phosphorylates a coat adaptor component, AP2M1, to help achieve this function. GAK is also implicated in Parkinson's disease through genome-wide association studies. However, GAK's role in mammalian neurons remains unclear, and insight may come from identification of further substrates. Employing a chemical genetics method, we show here that the sodium potassium pump (Na+/K+-ATPase) α-subunit Atp1a3 is a GAK target and that GAK regulates Na+/K+-ATPase trafficking to the plasma membrane. Whole-cell patch clamp recordings from CA1 pyramidal neurons in GAK conditional knockout mice show a larger change in resting membrane potential when exposed to the Na+/K+-ATPase blocker ouabain, indicating compromised Na+/K+-ATPase function in GAK knockouts. Our results suggest a modulatory role for GAK via phosphoregulation of substrates such as Atp1a3 during cargo trafficking.

Ubiquitination of neurotransmitter receptors and postsynaptic scaffolding proteins.

The human brain is made up of an extensive network of neurons that communicate by forming specialized connections called synapses. The amount, location, and dynamic turnover of synaptic proteins, including neurotransmitter receptors and synaptic scaffolding molecules, are under complex regulation and play a crucial role in synaptic connectivity and plasticity, as well as in higher brain functions. An increasing number of studies have established ubiquitination and proteasome-mediated degradation as universal mechanisms in the control of synaptic protein homeostasis. In this paper, we focus on the role of the ubiquitin-proteasome system (UPS) in the turnover of major neurotransmitter receptors, including glutamatergic and nonglutamatergic receptors, as well as postsynaptic receptor-interacting proteins.

AMPA receptors in the medial amygdala are critical for establishing a neuroendocrine memory in the female rat.

We sought to examine AMPA receptor (AMPAR) function in the medial posterodorsal amygdala (MePD), as glutamate neurotransmission is critical for the neural response to vaginal-cervical stimulation that initiates pregnancy or pseudopregnancy. Female rats were infused with the AMPAR antagonist CNQX or vehicle directly into the MePD via bilaterally implanted cannulae, then either returned to their homecage (HC), or received 15 mounts-without-intromissions (MO) or 15 intromissions (15I) from a male. Expression of the activity marker EGR-1 was used to determine the CNQX concentration which would prevent mating-induced activation of MePD neurons. Separate cannulated females received CNQX infusions into the MePD prior to receiving 15I, and the oestrous cycle length was monitored by daily vaginal lavages. Infusion of CNQX (500 nm) blocked mating-induced neural activation and lengthened the oestrous cycle, demonstrating AMPAR involvement in the formation of pseudopregnancy. To further explore this involvement, separate groups of 15I, MO and HC females were killed 90 min or 3 h after testing treatment. Brain sections were immunolabeled for AMPAR-subunit GluR1 phosphorylated at one of two sites (Serine-831 or Serine-845), or total GluR1 and GluR2, and immunofluorescence intensity was measured in the MePD, hippocampus and hypothalamus. A mating-induced increase in Serine-831 phosphorylation after 3 h was observed only in the MePD, whereas there was no effect on Serine-845 phosphorylation. Additionally, we observed a time-dependent increase in total GluR1 staining intensity. These results suggest an increased AMPAR function in the MePD after receipt of VCS, and a role for AMPAR in the neural response to VCS resulting in pseudopregnancy.

Hoxa10 and Hoxd10 coordinately regulate lumbar motor neuron patterning.

The paralogous Hox genes Hoxa10 and Hoxd10 are expressed in overlapping domains in the developing lumbar spinal cord and surrounding mesoderm. Independent inactivation of these two genes alters the trajectory of spinal nerves and decreases the complement of motor neurons present in the lumbar spinal cord, whereas dual inactivation of these two genes has been shown to alter peripheral nerve growth and development in the mouse hindlimb. We have examined the organization and distribution of lumbar motor neurons in the spinal cords of Hoxa10/Hoxd10 double mutant animals. Double mutant animals have decreased numbers of lumbar motor neurons in both the medial and lateral motor columns. The anteroposterior position of the lumbar motor column is shifted caudally in double mutant animals, and the distribution of motor neurons is altered across individual spinal segments. Distinctions between classes of motor neurons based on positional specificity appear disrupted in double mutants. Double mutants also demonstrate abnormal spinal cord vasculature and altered kidney placement and size. Our observations suggest that Hoxa10 and Hoxd10 activity is required to specify the position of the lumbar motor column and to provide segmental specification and identity for the lumbar motor neurons.