Incidental Findings from 16,400 Brain MRI Examinations of Research Volunteers.

BACKGROUND AND PURPOSE: Incidental findings are discovered in neuroimaging research, ranging from trivial to life-threatening. We describe the prevalence and characteristics of incidental findings from 16,400 research brain MRIs, comparing spontaneous detection by nonradiology scanning staff versus formal neuroradiologist interpretation. MATERIALS AND METHODS: We prospectively collected 16,400 brain MRIs (7782 males, 8618 females; younger than 1 to 94 years of age; median age, 38 years) under an institutional review board directive intended to identify clinically relevant incidental findings. The study population included 13,150 presumed healthy volunteers and 3250 individuals with known neurologic diagnoses. Scanning staff were asked to flag concerning imaging findings seen during the scan session, and neuroradiologists produced structured reports after reviewing every scan. RESULTS: Neuroradiologists reported 13,593/16,400 (83%) scans as having normal findings, 2193/16,400 (13.3%) with abnormal findings without follow-up recommended, and 614/16,400 (3.7%) with "abnormal findings with follow-up recommended." The most common abnormalities prompting follow-up were vascular (263/614, 43%), neoplastic (130/614, 21%), and congenital (92/614, 15%). Volunteers older than 65 years of age were significantly more likely to have scans with abnormal findings (P < .001); however, among all volunteers with incidental findings, those younger than 65 years of age were more likely to be recommended for follow-up. Nonradiologists flagged <1% of MRIs containing at least 1 abnormality reported by the neuroradiologists to be concerning enough to warrant further evaluation. CONCLUSIONS: Four percent of individuals who undergo research brain MRIs have an incidental, potentially clinically significant finding. Routine neuroradiologist review of all scans yields a much higher rate of significant lesion detection than selective referral from nonradiologists who perform the examinations. Workflow and scan review processes need to be carefully considered when designing research protocols.

Deep Brain Nuclei T1 Shortening after Gadobenate Dimeglumine in Children: Influence of Radiation and Chemotherapy.

BACKGROUND AND PURPOSE: Intrinsic T1-hyperintense signal has recently been reported in the deep gray nuclei on brain MR imaging after multiple doses of gadolinium-based contrast agents. Most reports have included adult patients and excluded those undergoing radiation or chemotherapy. We investigated whether T1 shortening is also observed in children and tried to determine whether radiochemotherapy is a risk factor for this phenomenon. MATERIALS AND METHODS: In this single-center retrospective study, we reviewed clinical charts and images of all patients 18 years of age or younger with ≥4 gadobenate dimeglumine-enhanced MRIs for 6 years. Seventy-six children (mean age, 9.3 years; 60 unconfounded by treatment, 16 with radiochemotherapy) met the selection criteria (>4 MR imaging examinations; mean, 8). T1 signal intensity ratios for the dentate to pons and globus pallidus to thalamus were calculated and correlated with number of injections, time interval, and therapy. RESULTS: Among the 60 children without radiochemotherapy, only 2 had elevated T1 signal intensity ratios (n = 20 and 16 injections). Twelve of the 16 children with radiochemotherapy showed elevated signal intensity ratios. Statistical analysis demonstrated a significant signal intensity ratio change for the number of injections (P < .001) and amount of gadolinium (P = .008), but not for the interscan time interval (P = .35). There was a significant difference in the average signal intensity ratio change between those with and without radiochemotherapy (P < .001). Chart review revealed no new neurologic deficits in any patients, related to their underlying conditions and prior surgeries. CONCLUSIONS: Compared with published adult series, children show a similar pattern of T1 hyperintense signal changes of the dentate and globus pallidus after multiple gadobenate dimeglumine injections. The T1 signal changes in children may have a later onset but are accelerated by radiochemotherapy.

The role of race in thyroid cancer: systematic review.

BACKGROUND: The incidence of thyroid cancer is increasing. There is conflicting evidence as to why. However, studies suggest that it is not an apparent increase resulting from enhanced diagnostic practices, but a true increase with more affected patients. This study aimed to assess racial variation in thyroid cancer. METHOD: A narrative systematic review of the literature was conducted. RESULTS: Eight retrospective cohort studies were identified, comprising 611 777 adult patients. Variations exist between racial groups, which are also dependent on gender; white patients have a slightly higher male population when compared to their counterparts. Black and white patients have a higher proportion of follicular cancer. Hispanics were younger at the age of diagnosis. Outcomes are greatly affected by socioeconomic status. CONCLUSION: This study identified many gaps in the way that these types of data are presented. A more concise manner of reporting, with individual-level risk factors, is recommended.

Gadolinium contrast agents for CNS imaging: current concepts and clinical evidence.

SUMMARY: The aim of this article was to review the properties of the various gadolinium-based contrast agents used for CNS imaging along with the clinical evidence and published data that highlight the impact these different properties can have on diagnostic performance. In addition, approaches to optimizing image acquisition that take into account the different properties of specific gadolinium-based contrast agents and an extensive review of the safety profiles of the various agents are presented.

Stroke service: how can we improve and measure outcomes? Consensus summary from a global stroke forum.

The success of acute stroke treatment is first and foremost time-dependent, and the need for improvement in acute stroke management is demonstrated by the fact that only a minority of patients gain access to treatment - in particular, intravenous recombinant tissue plasminogen activator (IV tPA) - within the necessary time window. Standards of acute stroke care vary widely both regionally and nationally; consequently, various healthcare organizations have undertaken initiatives to measure and improve quality of care. To date, most quality measures have been process-based, focusing primarily on metrics of patient care in the acute hospital-based setting (e.g., time to recombinant tPA administration). Therefore, there remains a need for metrics designed to assess how improvements in process translate into patient outcomes. A global forum was convened to share best practice and provide consensus recommendations on core metrics for measuring improvements in access to care and patient outcomes. Recommendations for core metrics of patient outcomes include hospital-based outcomes (e.g., neurological status at 24 h, ambulatory status at discharge) and post-discharge outcomes (e.g., modified Rankin Scale score at 30 and/or 90 days). Recommendations for best practice relating to aspects of people, process, and technology involved in the stroke treatment pathway that may help provide improvements in these core outcome measures are also outlined.

Cross-neutralization studies with salmonid alphavirus subtype 1-6 strains: results with sera from experimental studies and natural infections.

The serological reactivity between strains of each of the six currently genetically defined subtypes of salmonid alphavirus (SAV) was examined by comparison of homologous and heterologous virus neutralization titres on sera from experimentally infected fish. With the exception of the level of SAV subtype 6 neutralization by heterologous sera, good cross-neutralization was detected between all subtypes, albeit with variation in geometric mean titres when each subtype-specific serum set was tested against the panel of virus subtypes. A similar pattern was evident with field sera, except that heterologous neutralization of the SAV6 strain was more evident. In only 23% of available pairwise comparisons was the homologous titre recorded with an experimentally derived serum fourfold or greater than the heterologous titre, and in only two instances was this difference demonstrated in both directions. No virus strains consistently met the old serology-based criteria (Sub-committee on Inter-relationships Among Catalogued Alphaviruses) to be considered separate subtypes within an alphavirus species. Only when testing with an SAV subtype-2-specific monoclonal antibody was a major difference between homologous and heterologous neutralization capacity evident. These results provide new direct or indirect information in terms of SAV classification, vaccine efficacy and the selection and validation of reagents for serological and immunological diagnostic purposes.

Imaging recommendations for acute stroke and transient ischemic attack patients: A joint statement by the American Society of Neuroradiology, the American College of Radiology, and the Society of NeuroInterventional Surgery.

SUMMARY: Stroke is a leading cause of death and disability worldwide. Imaging plays a critical role in evaluating patients suspected of acute stroke and transient ischemic attack, especially before initiating treatment. Over the past few decades, major advances have occurred in stroke imaging and treatment, including Food and Drug Administration approval of recanalization therapies for the treatment of acute ischemic stroke. A wide variety of imaging techniques has become available to assess vascular lesions and brain tissue status in acute stroke patients. However, the practical challenge for physicians is to understand the multiple facets of these imaging techniques, including which imaging techniques to implement and how to optimally use them, given available resources at their local institution. Important considerations include constraints of time, cost, access to imaging modalities, preferences of treating physicians, availability of expertise, and availability of endovascular therapy. The choice of which imaging techniques to employ is impacted by both the time urgency for evaluation of patients and the complexity of the literature on acute stroke imaging. Ideally, imaging algorithms should incorporate techniques that provide optimal benefit for improved patient outcomes without delaying treatment.

Patterns of internet use by parents of children attending a pediatric surgical service.

PURPOSE: The internet has revolutionised the way we search for information. We determined the level of internet use by parents of children attending general surgical services and identified trends in online information-seeking behaviour. METHODS: A questionnaire based on the work by Boston and Tassone was distributed to parents attending both the day surgical units and surgical outpatients department in a paediatric tertiary referral centre. RESULTS: There were 214 (82.3 %) questionnaires returned, with 82 (38.3 %) of respondents having searched the internet regarding their child's surgical issue. Access to a smartphone, a university education and private health insurance were factors that positively influenced online searching (p < 0.005). Of those respondents who searched the internet, 42 (51 %) felt that information they found online was understandable, while only 14 (17 %) admitted to online sourced information influencing the treatment decisions they had made for their children. When asked to rank information sources on Likert-type scales in terms of importance; parents ranked the surgeon as most important (mean = 4.73), whilst the internet ranked lowest (mean = 3.02). CONCLUSION: We demonstrated significant use of the internet amongst those attending paediatric general surgical services. Clinician sourced information remains important, however we should engage with patients to utilise this vast resource effectively.

Division of tongue tie: review of practice through a tertiary paediatric otorhinolaryngology service.

OBJECTIVES: Recent NICE guidance declared that evidence regarding surgical division of tongue tie was adequate to support the use of the procedure, provided that normal arrangements are in place for consent, audit and clinical governance. This work aimed to carry out a retrospective review of those patients who have previously undergone tongue tie division through a tertiary paediatric otorhinolaryngology service. We further aimed to identify the referral patterns, indications for, and outcomes following, division. METHODS: A retrospective chart review of all patients attending for division of tongue-tie between January 2010 and June 2011, inclusive. RESULTS: A total of 48 patients underwent division of tongue-tie over the study period. The median age of patients at the time of operation was 16 months (range 3-192). Delayed speech or articulation problems (27%), and parental concern (23%) were the most common reasons for referral. Overt difficulty with feeding was responsible for referral in just 4 cases. All cases were performed under general anaesthetic as day-case procedures; 7 patients had a second procedure performed at the same time. No complications, either early or late, were recorded across this cohort. CONCLUSIONS: Tongue-tie division is a safe procedure with minimal associated morbidity. Whilst the primary indication cited in the literature is that of feeding difficulty, it appears that the majority of division is performed for other reasons.

Lisdexamfetamine and immediate release d-amfetamine - differences in pharmacokinetic/pharmacodynamic relationships revealed by striatal microdialysis in freely-moving rats with simultaneous determination of plasma drug concentrations and locomotor activity.

Lisdexamfetamine mesylate (Vyvanse(®)) is a novel prodrug approved for attention deficit hyperactivity disorder (ADHD). It is metabolised to d-amfetamine and l-lysine. In drug-experienced humans, lisdexamfetamine evoked lower "Drug liking" scores on Drug Rating Questionnaire (DRQ) scales than immediate-release (IR) d-amfetamine. This study investigated why lisdexamfetamine may have lower abuse potential and a better therapeutic window than d-amfetamine. We compared the pharmacokinetic/pharmacodynamic relationships of lisdexamfetamine and IR d-amfetamine in freely-moving rats by measuring simultaneously extracellular concentrations of striatal dopamine, plasma concentrations of d-amfetamine and lisdexamfetamine, and locomotor activity. At equivalent doses (1.5 mg/kg d-amfetamine base), lisdexamfetamine produced smaller, but more sustained, increases in striatal dopamine efflux than d-amfetamine and substantially less locomotor activation. Consistent with it being a prodrug, increased striatal dopamine and locomotion correlated with plasma concentration of its metabolite, d-amfetamine, but not the parent compound. Compared with IR d-amfetamine, lisdexamfetamine produced an identical AUC for plasma d-amfetamine, but a 50% lower C(max) and significantly delayed t(max). Where a hysteresis relationship did exist between plasma concentrations of d-amfetamine and striatal dopamine or locomotor activity, they were anticlockwise in direction for lisdexamfetamine and IR d-amfetamine. For extracellular striatal dopamine (neurochemical mediator) and locomotor activity (functional outcome), it was anticlockwise for lisdexamfetamine, but clockwise for IR d-amfetamine. This shows that lisdexamfetamine produced less pronounced behavioural activation as dopamine concentrations increased, but activity was maintained for longer when they declined. These findings help explain why the unusual pharmacokinetics of lisdexamfetamine evoked lower "Drug liking" scores than IR d-amfetamine and also suggest therapeutic window between efficacy and stimulant side-effects will be larger.

Geographical distribution of salmonid alphavirus subtypes in marine farmed Atlantic salmon, Salmo salar L., in Scotland and Ireland.

Sequence data from salmonid alphavirus (SAV) strains obtained from farmed marine Atlantic salmon, Salmo salar L. , over a 20-year period between 1991 and 2011 was reviewed to examine the geographical distribution of the genetically defined SAV subtypes in twelve regions across Ireland and Scotland. Of 160 different Atlantic salmon SAV strains examined, 62 belonged to subtype 1, 28 to subtype 2, 34 to subtype 4, 35 to subtype 5 and 1 to subtype 6. SAV subtypes 1, 4 and 6 were found in Ireland, while subtypes 1, 2, 4 and 5 were found in Scotland. In the majority of regions, there was a clear clustering of subtypes, with SAV subtype 1 being the dominant subtype in Ireland overall, as well as in Argyll and Bute in Scotland. SAV subtype 2 predominated in the Shetland and Orkney Islands. The emergence in Atlantic salmon of subtype 2 strains typically associated with sleeping disease in rainbow trout in Argyll and Bute, strongly suggesting transmission of infection between these species, was noted for the first time. SAV subtype 4 was the most common subtype found in the southern Western Isles, while SAV subtype 5 predominated in the northern Western Isles and north-west mainland Scotland. No single strain was dominant on sites in the western Highlands, with a number of sites in this region in particular having more than one subtype detected in different submissions. The significance of these results in relation to aspects of the epidemiology of infection, including transmission, biosecurity and wildlife reservoirs are discussed and knowledge gaps identified.

Family history of Alzheimer disease predicts hippocampal atrophy in healthy middle-aged adults.

OBJECTIVE: To evaluate the longitudinal influence of family history (FH) of Alzheimer disease (AD) and apolipoprotein E ε4 allele (APOE4) on brain atrophy and cognitive decline over 4 years among asymptomatic middle-aged individuals. METHODS: Participants were cognitively healthy adults with (FH+) (n = 60) and without (FH-) (n = 48) a FH of AD (mean age at baseline 54 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention. They underwent APOE genotyping, cognitive testing, and an MRI scan at baseline and 4 years later. A covariate-adjusted voxel-based analysis interrogated gray matter (GM) modulated probability maps at the 4-year follow-up visit as a function of FH and APOE4. We also examined the influence of parent of origin on GM atrophy. Parallel analyses investigated the effects of FH and APOE4 on cognitive decline. RESULTS: Neither FH nor APOE4 had an effect on regional GM or cognition at baseline. Longitudinally, a FH × APOE4 interaction was found in the right posterior hippocampus, which was driven by a significant difference between the FH+ and FH- subjects who were APOE4-. In addition, a significant FH main effect was observed in the left posterior hippocampus. No significant APOE4 main effects were detected. Persons with a maternal history of AD were just as likely as those with a paternal history of AD to experience posterior hippocampal atrophy. There was no longitudinal decline in cognition within the cohort. CONCLUSION: Over a 4-year interval, asymptomatic middle-aged adults with FH of AD exhibit significant atrophy in the posterior hippocampi in the absence of measurable cognitive changes. This result provides further evidence that detectable disease-related neuroanatomic changes do occur early in the AD pathologic cascade.

Vascular rings and slings: interesting vascular anomalies.

INTRODUCTION: A vascular ring refers to encirclement of the trachea and oesophagus by an abnormal combination of derivatives of the aortic arch system. These malformations can cause variable degrees of compression of the oesophagus, trachea or both. Symptoms can range from no effect to severe stridor, dyspnoea and/or dysphagia. METHOD AND RESULTS: This study presents a case series of six patients treated over a six-year period (2003-2009), illustrating the features of four different types of vascular ring; these types are discussed in detail. The clinical presentation, radiology, and microlaryngoscopy and bronchoscopy findings are also discussed. CONCLUSION: The management of children with vascular rings requires a high index of clinical suspicion to ensure prompt diagnosis. As many of these children present with airway symptoms, the paediatric otolaryngologist plays a key role in identifying and assessing their anatomical anomalies.

Pierre Robin sequence: an institutional experience in the multidisciplinary management of airway, feeding and serous otitis media challenges.

OBJECTIVES: To evaluate the course and prognosis of airway obstruction, feeding difficulties and hearing abnormalities in patients with Pierre Robin sequence (PRS). METHODS: A retrospective review was conducted, of 69 patients with PRS, attending between 1991 and 2010 at the Children's University Hospital in Dublin. Data regarding airway management, nutritional status and hearing difficulties was collected prospectively. RESULTS: Airway obstruction requiring intervention other than positional therapy was seen in 39% (27) patients. Fifty nine percent (16/27) of these patients, who failed positional therapy, were successfully managed with a nasopharyngeal airway. Following failed intervention with nasopharyngeal airways, two patients had airway maintenance achieved with a successful glossopexy procedure. One patient had an adequate airway achieved with nasal continuous positive airway pressure. Eight patients (12%) required a surgical tracheostomy. Of those who required a tracheostomy, six patients had isolated PRS, one patient had PRS in association with Stickler syndrome and one patient had Nager acro-facial dystosis. Duration of tracheostomy tube ranged from 10 to 19 months, mean 13 months. Seventy percent (48 patients) required supplementary feeding in the form of nasogastric (NG) or gastrostomy tube. Forty-four patients were successfully managed with a temporary NG tube. One patient required a prolonged NG tube, and three required a gastrostomy tube. Twenty-one (30%) patients were successfully managed with a specialised Haberman bottle. Twenty-four patients (35%) who had their airway managed successfully by positional therapy, still required supplemental feeding. Thirty-one patients (45%) demonstrated a conductive hearing loss at some stage, which affected their speech and language development. Twenty-four patients (35%) required tympanostomy tube insertion once, while 7 (10%) of patients required ventilation tube insertion twice or more. CONCLUSION: Airway management in the majority of PRS can be successfully achieved by conservative methods. Even in the presence of an adequate airway, many patients will require supplemental feeding. Early audiological assessment is necessary as many patients will need tympanostomy tube placement to ensure adequate speech and language development.

A comparative study of marine salmonid alphavirus subtypes 1-6 using an experimental cohabitation challenge model.

A comparative challenge study of six marine isolates representing subtypes 1-6 of salmonid alphavirus (salmon pancreas disease virus, Genus Alphavirus, Family Togaviridae) was conducted in Atlantic salmon in a fresh water cohabitation trial. Histopathological lesions typical of pancreas disease were observed with all subtypes, and virus was re-isolated from serum of cohabitant fish in each case. Using a virus neutralization (VN) test neutralizing salmonid alphavirus (SAV) subtype 1 strain F93-125, VN antibodies were detected in all challenge groups, consistent with serological cross-reactivity between these subtypes. Using real-time RT-PCR, SAV RNA was detected in heart tissue from 2 to 3 weeks post-challenge (wpc) in all cohabitant groups excluding controls. The results obtained suggested differences in the dynamics of infection between strains of SAV and potentially between subtypes. Results for SAV subtypes 1 and 3 suggested essentially synchronous infection of cohabitant fish. These two study groups also had the highest virus load in heart tissue as measured by quantitative RT-PCR and also had the most extensive histopathological changes. In contrast, results for SAV subtypes 2 and 6 strains were consistent with asynchronous infection in the cohabitant fish and were characterized by slow spread, low virus loads and mild histopathological changes. The SAV subtype 4 and 5 strains occupied an intermediate position in this regard. Despite the use of concentration procedures, it was not possible to detect SAV RNA in water samples from selected study tanks. However, testing of faeces from the SAV subtypes 1, 3 and 6 challenge groups found positive signals in each beginning at 1-3 wpc and remaining detectable for a further 2-3 weeks. Parallel testing of mucus samples found these became positive at 2-3 wpc and remained positive for a further 1-3 weeks. These results demonstrate for the first time that shedding and transmission of virus may occur by both these routes and suggest that dispersal in these matrices should be included in any disease transmission models.

Velocity measurements in the middle cerebral arteries of healthy volunteers using 3D radial phase-contrast HYPRFlow: comparison with transcranial Doppler sonography and 2D phase-contrast MR imaging.

BACKGROUND AND PURPOSE: We have developed PC HYPRFlow, a comprehensive MRA technique that includes a whole-brain CE dynamic series followed by PC velocity-encoding, yielding a time series of high-resolution morphologic angiograms with associated velocity information. In this study, we present velocity data acquired by using the PC component of PC HYPRFlow (PC-VIPR). MATERIALS AND METHODS: Ten healthy volunteers (6 women, 4 men) were scanned by using PC HYPRFlow and 2D-PC imaging, immediately followed by velocity measurements by using TCD. Velocity measurements were made in the M1 segments of the MCAs from the PC-VIPR, 2D-PC, and TCD examinations. RESULTS: PC-VIPR showed approximately 30% lower mean velocity compared with TCD, consistent with other comparisons of TCD with PC-MRA. The correlation with TCD was r = 0.793, and the correlation of PC-VIPR with 2D-PC was r = 0.723. CONCLUSIONS: PC-VIPR is a technique capable of acquiring high-resolution MRA of diagnostic quality with velocity data comparable with TCD and 2D-PC. The combination of velocity information and fast high-resolution whole-brain morphologic angiograms makes PC HYPRFlow an attractive alternative to current MRA methods.

Fast whole-brain 4D contrast-enhanced MR angiography with velocity encoding using undersampled radial acquisition and highly constrained projection reconstruction: image-quality assessment in volunteer subjects.

We report on the image quality obtained by using fast contrast-enhanced whole-brain 4D radial MRA with 0.75-second temporal resolution, isotropic submillimeter spatial resolution, and velocity encoding (HYPRFlow). Images generated by HYPR-LR by using the velocity-encoded data as the constraining image were of diagnostic quality. In addition, we demonstrate that measurements of shear stress within the middle cerebral artery can be derived from the high-resolution 3D velocity data.