Key Elements of Clinical Magnetic Resonance Imaging Safety: It Takes a Village.

Magnetic resonance (MR) imaging-related injuries have continued to occur at an alarming rate during more than 3 decades of use. Persistently reported MR imaging-related injuries are caused by (1) radiofrequency thermal effect burns, (2) bruising from table top and coil-related mechanical injuries, (3) magnetic field-related support equipment malfunction, (4) magnetic field-related projectile trauma, (5) gradient switching noise hearing loss. A cohesive and educated MR imaging community under the guidance of a defined management structure is essential for monitoring and mitigating MR imaging risks. This article offers an approach for decreasing MR imaging-related injury risks.

Posterior reversible encephalopathy syndrome (PRES): Another imaging manifestation of COVID-19.

Neuroimaging manifestations of COVID-19 are being reported with increasing frequency with recent reports of associated atypical leukoencephalopathies. We add to this literature by describing a COVID-19 + patient who demonstrated imaging findings typical for posterior reversible encephalopathy syndrome (PRES). The inflammatory syndrome associated with novel corona virus infection has shown markedly increased levels of cytokines and inflammatory markers. This has also been described in a proposed mechanism for PRES, where elevated inflammatory markers result in endothelial injury causing interstitial fluid extravasation typical of PRES. We expect that other cases of PRES will be observed in this population given the scope of the Covid-19 pandemic.

A ten-year retrospective evaluation of acute flaccid myelitis at 5 pediatric centers in the United States, 2005-2014.

BACKGROUND: Acute flaccid myelitis (AFM) is a severe illness similar to paralytic poliomyelitis. It is unclear how frequently AFM occurred in U.S. children after poliovirus elimination. In 2014, an AFM cluster was identified in Colorado, prompting passive US surveillance that yielded 120 AFM cases of unconfirmed etiology. Subsequently, increased reports were received in 2016 and 2018. To help inform investigations on causality of the recent AFM outbreaks, our objective was to determine how frequently AFM had occurred before 2014, and if 2014 cases had different characteristics. METHODS: We conducted a retrospective study covering 2005-2014 at 5 pediatric centers in 3 U.S. regions. Possible AFM cases aged ≤18 years were identified by searching discharge ICD-9 codes and spinal cord MRI reports (>37,000). Neuroradiologists assessed MR images, and medical charts were reviewed; possible cases were classified as AFM, not AFM, or indeterminate. RESULTS: At 5 sites combined, 26 AFM cases were identified from 2005-2013 (average annual number, 3 [2.4 cases/100,000 pediatric hospitalizations]) and 18 from 2014 (12.6 cases/100,000 hospitalizations; Poisson exact p<0.0001). A cluster of 13 cases was identified in September-October 2014 (temporal scan p = 0.0001). No other temporal or seasonal trend was observed. Compared with cases from January 2005-July 2014 (n = 29), cases from August-December 2014 (n = 15) were younger (p = 0.002), more frequently had a preceding respiratory/febrile illness (p = 0.03), had only upper extremities involved (p = 0.008), and had upper extremity monoplegia (p = 0.03). The cases had higher WBC counts in cerebrospinal fluid (p = 0.013). CONCLUSION: Our data support emergence of AFM in 2014 in the United States, and those cases demonstrated distinctive features compared with preceding sporadic cases.

ACR guidance document on MR safe practices: Updates and critical information 2019.

The need for a guidance document on MR safe practices arose from a growing awareness of the MR environment's potential risks and adverse event reports involving patients, equipment, and personnel. Initially published in 2002, the American College of Radiology White Paper on MR Safety established de facto industry standards for safe and responsible practices in clinical and research MR environments. The most recent version addresses new sources of risk of adverse events, increases awareness of dynamic MR environments, and recommends that those responsible for MR medical director safety undergo annual MR safety training. With regular updates to these guidelines, the latest MR safety concerns can be accounted for to ensure a safer MR environment where dangers are minimized. Level of Evidence: 1 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020;51:331-338.

Meningocele Manqué Discovered During Filum Terminale Resection in Occult Tethered Cord Syndrome.

BACKGROUND: Meningocele manqué (MM) is characterized by tethering of the spinal cord, nerve roots, or filum terminale by fibrous attachments formed by atrophic or incomplete meningoceles. Patients with MM can present with symptoms of tethered cord syndrome (TCS). CASE DESCRIPTION: We present the case of an MM discovered incidentally during microsurgical resection of filum terminale for occult TCS. The MM was not visible on the preoperative magnetic resonance imaging (MRI) studies. After L2-L3 laminotomy, an extradural mass was appreciated adherent to the spinal dura, which was found to be an MM. The nerve roots of the cauda equina were found to protrude through the dura, consistent with tethered cauda equina. After microsurgical resection of the filum terminale, the tethered cauda nerve roots were stimulated, and redundant electromyographic signals were detected at both the left- and the right-sided muscles of the lower extremities. Microsurgical repair of the MM was performed, assuming that the patient's symptoms of TCS would also be explained by the MM and that her symptoms would likely have been incompletely addressed by filum terminale release alone. A review of the preoperative 3-dimensional constructive interference in steady state MRI sequence revealed pathological features at the L2-L3 level suspicious for our intraoperative findings of an MM. CONCLUSIONS: Surgeons planning filum terminale release for occult TCS should always be aware of the possibility of associated pathological features of tethering that might be overlooked. In retrospect, the detection of MM was enabled by the high-resolution 3-dimensional constructive interference in steady state MRI sequence. This finding advocates for the use of high-resolution MRI for patients undergoing evaluation for occult TCS to detect pathological features that might otherwise be undetected.

Complex Neurological Phenotype in Female Carriers of NHE6 Mutations.

Mutations in NHE6 (also termed SLC9A6) cause the X-linked neurological disorder Christianson syndrome (CS) in males. The purpose of this study was to examine the phenotypic spectrum of female carriers of NHE6 mutations. Twenty female carriers from 9 pedigrees were enrolled, ranging from approximately age 2 to 65. A subset of female carriers was assessed using standardized neuropsychological measures. Also, the association of NHE6 expression with markers of brain age was evaluated using 740 participants in the Religious Orders Study (ROS) and Rush Memory and Aging Project (MAP). A majority, but not all, female carriers demonstrated a deficit in at least one neurocognitive domain (85%). A recognizable neuropsychological profile emerged, revealing impairments in visuospatial function, attention, and executive function. Common neuropsychiatric diagnoses included: intellectual disability/developmental delay (20%), learning difficulties (31%), speech/language delays (30%), and attention-deficit/hyperactivity disorder (20%). Notable neurological diagnoses in aging CS female carriers include corticobasal degeneration and atypical parkinsonism. In postmortem brains from the ROS/MAP dataset of normal and pathological aging, decreased NHE6 expression was correlated with greater tau deposition. Our study provides an examination of the phenotypic range in female carriers of NHE6 mutations. The findings indicate that NHE6-related disease in females represents a new neurogenetic condition.

Prospective study of myelin water fraction changes after mild traumatic brain injury in collegiate contact sports.

OBJECTIVE: Mild traumatic brain injury (mTBI) in athletes, including concussion, is increasingly being found to have long-term sequelae. Current imaging techniques have not been able to identify early damage caused by mTBI that is predictive of long-term symptoms or chronic traumatic encephalopathy. In this preliminary feasibility study, the authors investigated the use of an emerging magnetic resonance imaging (MRI) technique, multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT), in visualizing acute and chronic white matter changes after mTBI in collegiate football and rugby players. METHODS: This study was a nonrandomized, nonblinded prospective trial designed to quantify changes in the myelin water fraction (MWF), used as a surrogate MRI measure of myelin content, in a group of male collegiate football and rugby players, classified here as a contact sport player (CSP) cohort, at the time of mTBI diagnosis and 3 months after injury when the acute symptoms of the injury had resolved. In addition, differences in the MWF between the CSP cohort and a control cohort of noncontact sport players (NCSPs) were quantified. T-tests and a threshold-free cluster enhancement (TFCE) statistical analysis technique were used to identify brain structures with significant changes in the MWF between the CSP and NCSP cohorts and between immediately postinjury and follow-up images obtained in the CSP cohort. RESULTS: Brain MR images of 12 right-handed male CSPs were analyzed and compared with brain images of 10 right-handed male NCSPs from the same institution. A comparison of CSP and NCSP baseline images using TFCE showed significantly higher MWFs in the bilateral basal ganglia, anterior and posterior corpora callosa, left corticospinal tract, and left anterior and superior temporal lobe (p < 0.05). At the 3-month follow-up examination, images from the CSP cohort still showed significantly higher MWFs than those identified on baseline images from the NCSP cohort in the bilateral basal ganglia, anterior and posterior corpora callosa, and left anterior temporal lobe, and also in the bilateral corticospinal tracts, parahippocampal gyrus, and bilateral juxtapositional (previously known as supplemental motor) areas (p < 0.05). In the CSP cohort, a t-test comparing the MWF at the time of injury and 3 months later showed a significant increase in the overall MWF at follow-up (p < 0.005). These increases were greatest in the bilateral basal ganglia and deep white matter. MWF decreases were seen in more superficial white matter (p < 0.005). CONCLUSIONS: In this preliminary study, MWF was found to be increased in the brains of CSPs compared with the brains of controls, suggesting acute/chronic MWF alterations in CSPs from previous injuries. Increases in the MWF were also demonstrated in the brains of CSPs 3 months after the players sustained an mTBI. The full clinical significance of an increased MWF and whether this reflects axon neuropathology or disorderly remyelination leading to hypermyelination has yet to be determined.

Prognostic value of contrast enhancement and FLAIR for survival in newly diagnosed glioblastoma treated with and without bevacizumab: results from ACRIN 6686.

Background: ACRIN 6686/RTOG 0825 was a phase III trial of conventional chemoradiation plus adjuvant temozolomide with bevacizumab or without (placebo) in newly diagnosed glioblastoma. This study investigated whether changes in contrast-enhancing and fluid attenuated inversion recovery (FLAIR)-hyperintense tumor assessed by central reading prognosticate overall survival (OS). Methods: Two hundred eighty-four patients (171 men; median age 57 y, range 19-79; 159 on bevacizumab) had MRI at post-op (baseline) and pre-cycle 4 of adjuvant temozolomide (22 wk post chemoradiation initiation). Four central readers measured bidimensional lesion enhancement (2D-T1) and FLAIR hyperintensity at both time points. Changes from baseline to pre-cycle 4 for both markers were dichotomized (increasing vs non-increasing). Cox proportional hazards model and Kaplan-Meier survival estimates were used for inference. Results: Adjusting for treatment, increasing 2D-T1 (n = 262, hazard ratio [HR] = 2.07, 95% CI: 1.48-2.91, P < 0.0001) and FLAIR (n = 273, HR = 1.75, 95% CI: 1.26-2.41, P = 0.0008) significantly predicted worse OS. Median OS (days) was significantly shorter for patients with increasing versus non-increasing 2D-T1 for both bevacizumab (443 vs 535, P = 0.004) and placebo (526 vs 887, P = 0.001). Median OS was significantly shorter for patients with increasing versus non-increasing FLAIR for placebo (595 vs 872, P = 0.001), and trended similarly for bevacizumab (499 vs 535, P = 0.0935). Adjusting for 2D-T1 and treatment, increasing FLAIR represented significantly higher risk for death (HR = 1.59 [1.11-2.26], P = 0.01). Conclusion: Increased 2D-T1 significantly predicts worse OS in both treatment groups, implying absence of a substantial proportion of pseudoprogression 22 weeks after initiation of standard therapy. FLAIR adds value beyond 2D-T1 in predicting OS, potentially addressing the pseudoresponse effect by substratifying bevacizumab-treated patients with non-increasing 2D-T1.

Adenoid cystic carcinoma presenting with bilateral orbital extension from the soft palate.

Adenoid cystic carcinoma (ACC) is a rare neoplasm of secretory epithelium that most commonly occurs in the fifth and sixth decades of life. It is characterized by high recurrence rates and poor response to chemotherapy, In the orbit, ACC usually presents as a lacrimal gland mass. We describe the rare case of a 70-year-old woman who presented with pain during mastication and bilateral facial numbness in the cranial nerve V2 distribution. She was found to have adenoid cystic carcinoma involving the orbits bilaterally without lacrimal gland involvement and without a clear primary tumor. Imaging suggested that the tumor arose from the soft palate by extension along cranial nerves V2 and V3. The patient was treated with radiation therapy with some degree of radiographic improvement 27 months after diagnosis. This case emphasizes the importance of considering adenoid cystic carcinoma when evaluating orbital tumors sparing the lacrimal gland. We also suggest the possibility of an oropharyngeal source with anterograde intracranial extension in cases of putative primary orbital ACC without lacrimal gland involvement.

Mechanical embolectomy for acute ischemic stroke beyond six hours from symptom onset using MRI based perfusion imaging.

INTRODUCTION: There is very limited data on the use of MRI based perfusion imaging to select patients with acute ischemic stroke and large vessel occlusion (LVO) for intraarterial therapy beyond 6h from onset. Our aim is to report the outcome of patients with acute ischemic stroke and large artery occlusion who presented beyond 6h from onset, had favorable MRI imaging profile, and underwent mechanical embolectomy. METHODS: This is a single institution (Rhode Island Hospital) retrospective study between December 1st, 2015, and July 30th, 2016 that included patients with acute ischemic stroke and proximal LVO with CT ASPECTS of 6 or more and 6-24h from symptom onset who were assessed for mechanical embolectomy using MRI based perfusion imaging. Favorable imaging profile was defined based on prior studies as 1) DWI lesion volume (as defined as apparent diffusion coefficient<620×10-6mm2/s) of 70ml or less; 2) Penumbra volume (as defined by volume of tissue with Tmax>6s) of 15ml or greater; 3) A mismatch ratio of 1.8 or more; and 4) Volume of tissue with perfusion lesion with Tmax>10s is <100ml. Good outcome was defined as a 90-day mRS≤2. RESULTS: 41 patients met the inclusion criteria; 22 (53.7%) had favorable imaging profile and underwent mechanical embolectomy. The rate of good outcomes in this series was similar to that in a patient level pooled meta-analysis of the recent endovascular trials (63.6% vs. 46%, p=0.13). None of the patients in our cohort had symptomatic intracereberal hemorrhage. CONCLUSIONS: MRI perfusion based imaging may help select patients with acute ischemic stroke and proximal emergent LVO for embolectomy beyond the treatment window used in most endovascular trials. This provides compelling evidence for stroke centers to participate in ongoing trials using advanced imaging to study endovascular treatment in this patient population.

Longitudinal DSC-MRI for Distinguishing Tumor Recurrence From Pseudoprogression in Patients With a High-grade Glioma.

OBJECTIVE: For patients with high-grade glioma on clinical trials it is important to accurately assess time of disease progression. However, differentiation between pseudoprogression (PsP) and progressive disease (PD) is unreliable with standard magnetic resonance imaging (MRI) techniques. Dynamic susceptibility contrast perfusion MRI (DSC-MRI) can measure relative cerebral blood volume (rCBV) and may help distinguish PsP from PD. METHODS: A subset of patients with high-grade glioma on a phase II clinical trial with temozolomide, paclitaxel poliglumex, and concurrent radiation were assessed. Nine patients (3 grade III, 6 grade IV), with a total of 19 enhancing lesions demonstrating progressive enhancement (≥25% increase from nadir) on postchemoradiation conventional contrast-enhanced MRI, had serial DSC-MRI. Mean leakage-corrected rCBV within enhancing lesions was computed for all postchemoradiation time points. RESULTS: Of the 19 progressively enhancing lesions, 10 were classified as PsP and 9 as PD by biopsy/surgery or serial enhancement patterns during interval follow-up MRI. Mean rCBV at initial progressive enhancement did not differ significantly between PsP and PD (2.35 vs. 2.17; P=0.67). However, change in rCBV at first subsequent follow-up (-0.84 vs. 0.84; P=0.001) and the overall linear trend in rCBV after initial progressive enhancement (negative vs. positive slope; P=0.04) differed significantly between PsP and PD. CONCLUSIONS: Longitudinal trends in rCBV may be more useful than absolute rCBV in distinguishing PsP from PD in chemoradiation-treated high-grade gliomas with DSC-MRI. Further studies of DSC-MRI in high-grade glioma as a potential technique for distinguishing PsP from PD are indicated.

Toxoplasmosis versus lymphoma: Cerebral lesion characterization using DSC-MRI revisited.

OBJECTIVE: CNS toxoplasmosis and lymphoma are often indistinguishable by conventional contrast-enhanced MRI. There is limited literature on the diagnostic efficacy of dynamic susceptibility contrast (DSC) MRI for differentiating these entities. This study assesses the clinical utility of relative cerebral blood volume (rCBV) for making a diagnosis and determines rCBV thresholds for differentiation using contemporary DSC-MRI. PATIENTS AND METHODS: Thirteen patients with 25 lesions (13 toxoplasmosis and 12 lymphoma) and pre-treatment DSC-MRI were identified retrospectively. Volumetric regions of interest of segmented enhancement were used to extract mean rCBV normalized to normal-appearing white matter for each lesion. We compared average mean rCBV between all toxoplasmosis and lymphoma lesions using a general mixed model. Three models were also compared for evaluating rCBV-based disease status in each patient: 1) mean rCBV of each lesion using a generalized estimating equation, 2) volume-weighted mean rCBV, and 3) maximum mean rCBV of all lesions using logistic regression. RESULTS: The average mean rCBV for all toxoplasmosis lesions was 0.98 (95% CI 0.55-1.41) compared to 2.07 (95% CI 1.71-2.43) for all lymphoma lesions, a significant difference (1.09, 95% CI 0.53-1.65, p=0.0013). For the three models used to evaluate rCBV-based disease status in each patient, a significant relationship was observed, with an optimal rCBV threshold of approximately 1.5 for distinguishing lymphoma from toxoplasmosis in each model. CONCLUSION: RCBV derived from contemporary DSC-MRI is helpful for distinguishing between cerebral toxoplasmosis and cerebral lymphoma on an individual patient basis and may facilitate more timely initiation of appropriate directed therapy.

Ipilimumab treatment associated pituitary hypophysitis: clinical presentation and imaging diagnosis.

Ipilimumab is an immunomodulating drug for use in treatment of unresectable or metastatic melanoma with autoimmune lymphocytic hypophysitis as a reported complication. We describe three recent cases of ipilimumab associated autoimmune hypophysitis (IAH) at our institution, and provide a selected literature review showing its variable clinical presentation, imaging appearance and treatment in order to expedite early and appropriate IAH management. Patients had variable clinical presentation of hypophysitis, including headache, fatigue, visual changes, endocrinopathy, and/or hyponatremia. Contrast enhanced MRI showed symmetric pituitary gland and stalk enlargement in all of our cases and received a presumptive diagnosis of IAH. Following cessation of therapy and treatment there was normalization of pituitary morphology at follow-up MRI and return to clinical baseline. Varying clinical presentation can complicate the diagnosis of lymphocytic hypophysitis. One must be cognizant of its overall clinical and radiologic picture in patients receiving ipilimumab, now commonly used for the treatment of metastatic melanoma.

Genetic and phenotypic diversity of NHE6 mutations in Christianson syndrome.

OBJECTIVE: Recently, Christianson syndrome (CS) has been determined to be caused by mutations in the X-linked Na(+) /H(+) exchanger 6 (NHE6). We aimed to determine the diagnostic criteria and mutational spectrum for CS. METHODS: Twelve independent pedigrees (14 boys, age = 4-19 years) with mutations in NHE6 were administered standardized research assessments, and mutations were characterized. RESULTS: The mutational spectrum was composed of 9 single nucleotide variants, 2 indels, and 1 copy number variation deletion. All mutations were protein-truncating or splicing mutations. We identified 2 recurrent mutations (c.1498 c>t, p.R500X; and c.1710 g>a, p.W570X). Otherwise, all mutations were unique. In our study, 7 of 12 mutations (58%) were de novo, in contrast to prior literature wherein mutations were largely inherited. We also report prominent neurological, medical, and behavioral symptoms. All CS participants were nonverbal and had intellectual disability, epilepsy, and ataxia. Many had prior diagnoses of autism and/or Angelman syndrome. Other neurologic symptoms included eye movement abnormalities (79%), postnatal microcephaly (92%), and magnetic resonance imaging evidence of cerebellar atrophy (33%). Regression was noted in 50%, with recurrent presentations involving loss of words and/or the ability to walk. Medical symptoms, particularly gastrointestinal symptoms, were common. Height and body mass index measures were below normal ranges in most participants. Behavioral symptoms included hyperkinetic behavior (100%), and a majority exhibited high pain threshold. INTERPRETATION: This is the largest cohort of independent CS pedigrees reported. We propose diagnostic criteria for CS. CS represents a novel neurogenetic disorder with general relevance to autism, intellectual disability, Angelman syndrome, epilepsy, and regression.

The Brown University Traumatic Brain Injury Research Consortium and the Norman Prince Neurosciences Institute.

This article provides an overview of the Brown University Traumatic Brain Injury Research Consortium (TBIRC) and summarizes the multidisciplinary basic and clinical neuroscience work being conducted by investigators at Brown University and the affiliate hospitals in association with the Norman Prince Neurosciences Institute (NPNI).

Prenatal MRI characterization of brainstem glioma.

We describe a unique case of prenatally diagnosed diffuse brainstem glioma, detected during routine obstetric ultrasound and characterized with fetal magnetic resonance imaging. The diagnosis was supported by early postpartum imaging and confirmed at autopsy. Few examples of these rare lesions have been described in neonates by imaging and fewer cases have been confirmed by histopathological examination. Our case contributes to the limited literature concerning the clinical, MRI, and pathological correlates of brainstem gliomas in the perinatal period.