Sophia Göricke

Guidelines for imaging retinoblastoma: imaging principles and MRI standardization

Retinoblastoma is the most common intraocular tumor in children. The diagnosis is usually established by the ophthalmologist on the basis of fundoscopy and US. Together with US, high-resolution MRI has emerged as an important imaging modality for pretreatment assessment, i.e. for diagnostic confirmation, detection of local tumor extent, detection of associated developmental malformation of the brain and detection of associated intracranial primitive neuroectodermal tumor (trilateral retinoblastoma). Minimum requirements for pretreatment diagnostic evaluation of retinoblastoma or mimicking lesions are presented, based on consensus among members of the European Retinoblastoma Imaging Collaboration (ERIC). The most appropriate techniques for imaging in a child with leukocoria are reviewed. CT is no longer recommended. Implementation of a standardized MRI protocol for retinoblastoma in clinical practice may benefit children worldwide, especially those with hereditary retinoblastoma, since a decreased use of CT reduces the exposure to ionizing radiation.

Diagnostic Performance of Magnetic Resonance Imaging and Computed Tomography for Advanced Retinoblastoma: A Systematic Review and Meta-analysis

PURPOSE To determine and compare the diagnostic performance of magnetic resonance imaging (MRI) and computed tomography (CT) for the diagnosis of tumor extent in advanced retinoblastoma, using histopathologic analysis as the reference standard. DESIGN Systematic review and meta-analysis. PARTICIPANTS Patients with advanced retinoblastoma who underwent MRI, CT, or both for the detection of tumor extent from published diagnostic accuracy studies. METHODS Medline and Embase were searched for literature published through April 2013 assessing the diagnostic performance of MRI, CT, or both in detecting intraorbital and extraorbital tumor extension of retinoblastoma. Diagnostic accuracy data were extracted from included studies. Summary estimates were based on a random effects model. Intrastudy and interstudy heterogeneity were analyzed. MAIN OUTCOME MEASURES Sensitivity and specificity of MRI and CT in detecting tumor extent. RESULTS Data of the following tumor-extent parameters were extracted: anterior eye segment involvement and ciliary body, optic nerve, choroidal, and (extra)scleral invasion. Articles on MRI reported results of 591 eyes from 14 studies, and articles on CT yielded 257 eyes from 4 studies. The summary estimates with their 95% confidence intervals (CIs) of the diagnostic accuracy of conventional MRI at detecting postlaminar optic nerve, choroidal, and scleral invasion showed sensitivities of 59% (95% CI, 37%-78%), 74% (95% CI, 52%-88%), and 88% (95% CI, 20%-100%), respectively, and specificities of 94% (95% CI, 84%-98%), 72% (95% CI, 31%-94%), and 99% (95% CI, 86%-100%), respectively. Magnetic resonance imaging with a high (versus a low) image quality showed higher diagnostic accuracies for detection of prelaminar optic nerve and choroidal invasion, but these differences were not statistically significant. Studies reporting the diagnostic accuracy of CT did not provide enough data to perform any meta-analyses. CONCLUSIONS Magnetic resonance imaging is an important diagnostic tool for the detection of local tumor extent in advanced retinoblastoma, although its diagnostic accuracy shows room for improvement, especially with regard to sensitivity. With only a few-mostly old-studies, there is very little evidence on the diagnostic accuracy of CT, and generally these studies show low diagnostic accuracy. Future studies assessing the role of MRI in clinical decision making in terms of prognostic value for advanced retinoblastoma are needed.

Activation of the cerebellar cortex and the dentate nucleus in a prism adaptation fMRI study

During prism adaptation two types of learning processes can be distinguished. First, fast strategic motor control responses are predominant in the early course of prism adaptation to achieve rapid error correction within few trials. Second, slower spatial realignment occurs among the misaligned visual and proprioceptive sensorimotor coordinate system. The aim of the present ultra‐highfield (7T) functional magnetic resonance imaging (fMRI) study was to explore cerebellar cortical and dentate nucleus activation during the course of prism adaptation in relation to a similar visuomotor task without prism exposure. Nineteen young healthy participants were included into the study. Recently developed normalization procedures were applied for the cerebellar cortex and the dentate nucleus. By means of subtraction analysis (early prism adaptation > visuomotor, early prism adaptation > late prism adaptation) we identified ipsilateral activation associated with strategic motor control responses within the posterior cerebellar cortex (lobules VIII and IX) and the ventro‐caudal dentate nucleus. During the late phase of adaptation we observed pronounced activation of posterior parts of lobule VI, although subtraction analyses (late prism adaptation > visuomotor) remained negative. These results are in good accordance with the concept of a representation of non‐motor functions, here strategic control, within the ventro‐caudal dentate nucleus. Hum Brain Mapp 35:1574–1586, 2014.

A cerebellar role in performance monitoring - evidence from EEG and voxel-based morphometry in patients with cerebellar degenerative disease.

The cerebellum applies an internal forward-model to predict the sensory consequences of actions. This forward-model is updated based on on-line performance monitoring. A previous study has shown that performance monitoring is altered in patients with focal vascular cerebellar lesions, but altered neural responses are not paralleled by impaired behaviour, and the critical cerebellar sites have yet to be identified. The present study investigated if saccadic performance monitoring is more severely altered in patients with cerebellar degenerative disease relative to the previously examined patients with focal vascular cerebellar lesions, and which cerebellar regions support performance monitoring. 16 patients and 16 healthy controls performed an antisaccade task while an electroencephalogram (EEG) was recorded. Error rates were increased, and the error-related negativity (ERN), an event-related potential (ERP) component associated with error processing/performance monitoring, was reduced while the error positivity (Pe), a later ERP component related to more conscious aspects of error processing, was preserved in patients. Thus, performance monitoring is altered in patients with cerebellar degeneration, confirming a critical role of the cerebellum for fast classification of saccadic accuracy. In contrast to patients with focal lesions, post-acute functional reorganization and compensation presumably is hampered by disease progression, resulting in altered neural processing and impaired behavioural performance. Voxel-based morphometry (VBM) indicated the strongest effects for behavioural performance, with correlations between gray matter volume reduction in bilateral posterolateral regions (left Crus II and right lobule VI) and increased error rates. Moreover, somewhat smaller correlations were found for volume loss in left lobule VIIb/VIIIa and right lobule V and ERN amplitude, and in right Crus I and Pe amplitude. The present findings are consistent with involvement of posterolateral cerebellar regions in motor and cognitive functions.

Storage of a naturally acquired conditioned response is impaired in patients with cerebellar degeneration

Previous findings suggested that the human cerebellum is involved in the acquisition but not the long-term storage of motor associations. The finding of preserved retention in cerebellar patients was fundamentally different from animal studies which show that both acquisition and retention depends on the integrity of the cerebellum. The present study investigated whether retention had been preserved because critical regions of the cerebellum were spared. Visual threat eye-blink responses, that is, the anticipatory closure of the eyes to visual threats, have previously been found to be naturally acquired conditioned responses. Because acquisition is known to take place in very early childhood, visual threat eye-blink responses can be used to test retention in patients with adult onset cerebellar disease. Visual threat eye-blink responses were tested in 19 adult patients with cerebellar degeneration, 27 adult patients with focal cerebellar lesions due to stroke, 24 age-matched control subjects, and 31 younger control subjects. High-resolution structural magnetic resonance images were acquired in patients to perform lesion–symptom mapping. Voxel-based morphometry was performed in patients with cerebellar degeneration, and voxel-based lesion–symptom mapping in patients with focal disease. Visual threat eye-blink responses were found to be significantly reduced in patients with cerebellar degeneration. Visual threat eye-blink responses were also reduced in patients with focal disease, but to a lesser extent. Visual threat eye-blink responses declined with age. In patients with cerebellar degeneration the degree of cerebellar atrophy was positively correlated with the reduction of conditioned responses. Voxel-based morphometry showed that two main regions within the superior and inferior parts of the posterior cerebellar cortex contributed to expression of visual threat eye-blink responses bilaterally. Involvement of the more inferior parts of the posterior lobe was further supported by voxel-based lesion symptom mapping in focal cerebellar patients. The present findings show that the human cerebellar cortex is involved in long-term storage of learned responses.

Imaging of Electrode Position after Cochlear Implantation with Flat Panel CT

Background. Postoperative imaging after cochlear implantation is usually performed by conventional cochlear view (X-ray) or by multislice computed tomography (MSCT). MSCT after cochlear implantation often provides multiple metal artefacts; thus, a more detailed view of the implant considering the given anatomy is desirable. A quite new method is flat panel volume computed tomography. The aim of the study was to evaluate the methods clinical use. Material and Methods. After cochlear implantation with different implant types, flat panel CT scan (Philips Allura) was performed in 31 adult patients. Anatomical details, positioning, and resolution of the different electrode types (MedEL, Advanced Bionics, and Cochlear) were evaluated interdisciplinary (ENT/Neuroradiology). Results. In all 31 patients cochlear implant electrode array and topographical position could be distinguished exactly. Spatial resolution and the high degree of accuracy were superior to reported results of MSCT. Differentiation of cochlear scalae by identification of the osseous spiral lamina was possible in some cases. Scanning artefacts were low. Conclusion. Flat panel CT scan allows exact imaging independent of implant type. This is mandatory for detailed information on cochlear electrode position. It enables us to perform optimal auditory nerve stimulation and allows feed back on surgical quality concerning the method of electrode insertion.

Association of aneurysms and variation of the A1 segment

Background and purpose Previous studies have described a correlation between variants of the circle of Willis and pathological findings, such as cerebrovascular diseases. Moreover, anatomic variations of the anterior cerebral artery (ACA) seem to correspond to the prevalence of aneurysms in the anterior communicating artery (ACoA). The aim of this study was to assess the prevalence of aneurysms in patients with anatomical/morphological variations of the circle of Willis. Methods We retrospectively analyzed 223 patients who underwent cerebral angiography between January 2002 and December 2010 for aneurysm of the ACoA. Diagnostic imaging was reviewed and statistically evaluated to detect circle of Willis anomalies, aneurysm size, and rupture. 204 patients with an unrelated diagnosis served as the control group. Results Variations of the A1 segment occurred significantly more frequently in the aneurysm group than in the control group. Mean aneurysm size in patients with grades I and III hypoplasia or aplasia was 6.58 mm whereas in patients with grade II hypoplasia it was 7.76 mm. Conclusions We found that variations in the A1 segment of the ACAs are correlated with a higher prevalence of ACoA aneurysms compared with patients with a symmetric circle of Willis.

The potential of 3T high-resolution magnetic resonance imaging for diagnosis, staging, and follow-up of retinoblastoma

We demonstrate the value of high-resolution magnetic resonance imaging (MRI) in diagnosing, staging, and follow-up of retinoblastoma during eye-saving treatment. We have included informative retinoblastoma cases scanned on a 3T MRI system from a retrospective retinoblastoma cohort from 2009 through 2013. We show that high-resolution MRI has the potential to detect small intraocular seeds, hemorrhage, and metastatic risk factors not visible with fundoscopy (e.g., optic nerve invasion and choroidal invasion), and treatment response. Unfortunately, however, the diagnostic accuracy of high-resolution MRI is not perfect, especially for subtle intraocular seeds or minimal postlaminar optic nerve invasion. The most important application of MRI is the detection of metastatic risk factors, as these cannot be found by fundoscopy and ultrasound.

Age effects in storage and extinction of a naturally acquired conditioned eyeblink response.

Acquisition of conditioned eyeblink responses is known to decline with age, and age-related decline has been related to a reduction of cerebellar size and function. The aim of the present study was to investigate age-related effects on storage-related processes and extinction of visual threat eyeblink responses (VTERs), conditioned responses which are naturally acquired in early childhood. Storage and extinction of VTERs were tested in 34 healthy participants with an age range from 21 to 74 years (mean age 41.6±16.3 years). High-resolution structural magnetic resonance images (MRI) were acquired in all subjects. Conventional volumetric measures and voxel-based morphometry (VBM) were performed at the level of the cerebellum. Storage and extinction of VTERs showed a significant age-dependent decline. Likewise, cerebellar volume decreased with age. Storage, but not extinction showed a significant positive correlation with age-dependent reduction of total cerebellar volume. VBM analysis showed that gray matter volume in circumscribed areas of intermediate lobules VI, and Crus I and II bilaterally were positively correlated with VTER storage (p<0.05, FWE corrected). Considering extinction, no significant correlations with gray matter cerebellar volume were observed. The present findings show that reduction of storage of learned eyeblink responses with age is explained at least in part by age-dependent decline of cerebellar function. Future studies need to be performed to better understand which brain areas contribute to age-dependent reduction of extinction.

Pronounced reduction of acquisition of conditioned eyeblink responses in young adults with focal cerebellar lesions impedes conclusions on the role of the cerebellum in extinction and savings

Human cerebellar lesion studies provide good evidence that the cerebellum contributes to the acquisition of classically conditioned eyeblink responses (CRs). As yet, only one study used more advanced methods of lesion-symptom (or lesion-behavior) mapping to investigate which cerebellar areas are involved in CR acquisition in humans. Likewise, comparatively few studies investigated the contribution of the human cerebellum to CR extinction and savings. In this present study, young adults with focal cerebellar disease were tested. A subset of participants was expected to acquire enough conditioned responses to allow the investigation of extinction and saving effects. 19 participants with chronic surgical lesions of the cerebellum and 19 matched control subjects were tested. In all cerebellar subjects benign tumors of the cerebellum had been surgically removed. Eyeblink conditioning was performed using a standard short delay protocol. An initial unpaired control phase was followed by an acquisition phase, an extinction phase and a subsequent reacquisition phase. Structural 3T magnetic resonance images of the brain were acquired on the day of testing. Cerebellar lesions were normalized using methods optimized for the cerebellum. Subtraction analysis and Liebermeister tests were used to perform lesion-symptom mapping. As expected, CR acquisition was significantly reduced in cerebellar subjects compared to controls. Reduced CR acquisition was significantly more likely in participants with lesions of lobule VI and Crus I extending into Crus II (p<0.05, Liebermeister test). Cerebellar subjects could be subdivided into two groups: a smaller group (n=5) which showed acquisition, extinction and savings within the normal range; and a larger group (n=14) which did not show acquisition. In the latter, no conclusions on extinction or savings could be drawn. Previous findings were confirmed that circumscribed areas in lobule VI and Crus I are of major importance in CR acquisition. In addition, the present data suggest that if the critical regions of the cerebellar cortex are lesioned, the ability to acquire CRs is not only reduced but abolished. Subjects with lesions outside these critical areas, on the other hand show preserved acquisition, extinction and saving effects. As a consequence, studies in human subjects with cerebellar lesions do not allow drawing conclusions on CR extinction and savings. In light of the present findings, previous reports of reduced extinction in humans with circumscribed cerebellar disease need to be critically reevaluated.