Where does the gadolinium go? A review into the excretion and retention of intravenous gadolinium.

Gadolinium-based contrast agents (GBCAs) are commonly used in medical imaging. Most intravenously (IV) administered gadolinium is excreted via the kidneys, and pathological retention in renal failure leading to nephrogenic systemic fibrosis (NSF) is well described. More recently, retention of gadolinium in the body in the absence of renal disease has been identified, with unknown clinical consequences. Many patients are aware of this, either through the media or via comprehensive consent documentation. Some internet sites, without hard evidence, have suggested a constellation of possible symptoms associated with GBCA retention. Recent experience with patients ascribing symptoms to a contrast-enhanced MRI examination prompted this review of the fate of injected GBCA after MRI study, and of information available to patients online regarding gadolinium retention.

Intracranial perianeurysmal cysts: case series and review of the literature.

BACKGROUND: Intracranial perianeurysmal cysts are a rare finding associated with cerebral aneurysms. Patients may present with symptoms secondary to mass effect from perianeurysmal cysts requiring drainage. These lesions can masquerade as neoplasms if dedicated vascular imaging is not performed, leading to misdiagnosis. METHOD: A retrospective search of our database was done for intracranial aneurysms that have been treated between 1998 and 2020. A literature search was then performed on PubMed and Google Scholar with the search terms 'aneurysm', 'intracranial/intracerebral', 'cyst', and 'perianeurysmal cyst'. Patient demographics, aneurysms and cysts characteristics were then summarized as a table and in the discussion. RESULTS: Three cases where intracranial aneurysm had associated perianeurysmal cysts were found in our database. Combined with the available literature a total of 19 cases of perianeurysmal cysts have thus far been reported since this entity was first described in 2002. A significant number of perianeurysmal cysts (5/19) required intervention. In 5/19 cases the patient presented with a perianeurysmal cyst without a history of subarachnoid hemorrhage. Of the 10 cases where aneurysm follow-up was reported there were 5 cases where there was aneurysm recurrence necessitating re-treatment. CONCLUSION: Significant variability exists in the patient demographics, aneurysm and cyst characteristics of perianeurysmal cysts. This suggests that there is no single unified etiology and pathogenesis. These lesions are a rare finding and at present do not appear to carry diagnostic or prognostic significance. Management of perianeurysmal cysts is case-dependent and intervention should be considered when treating the related aneurysm, especially in patients with secondary symptoms.

Standards of practice in acute ischemic stroke intervention: International recommendations.

This article was first published in JNIS. Cite this article as: Pierot L, Jayaraman MV, Szikora I, et al. Standards of practice in acute ischemic stroke intervention: international recommendations. Journal of NeuroInterventional Surgery. Published Online First: 28 August 2018. doi: 10.1136/neurintsurg-2018-014287.

Epstein-Barr virus-specific T cell therapy for progressive multiple sclerosis.

BACKGROUND: Increasing evidence indicates a role for EBV in the pathogenesis of multiple sclerosis (MS). EBV-infected autoreactive B cells might accumulate in the CNS because of defective cytotoxic CD8+ T cell immunity. We sought to determine the feasibility and safety of treating progressive MS patients with autologous EBV-specific T cell therapy. METHODS: An open-label phase I trial was designed to treat 5 patients with secondary progressive MS and 5 patients with primary progressive MS with 4 escalating doses of in vitro-expanded autologous EBV-specific T cells targeting EBV nuclear antigen 1, latent membrane protein 1 (LMP1), and LMP2A. Following adoptive immunotherapy, we monitored the patients for safety and clinical responses. RESULTS: Of the 13 recruited participants, 10 received the full course of T cell therapy. There were no serious adverse events. Seven patients showed improvement, with 6 experiencing both symptomatic and objective neurological improvement, together with a reduction in fatigue, improved quality of life, and, in 3 patients, reduced intrathecal IgG production. All 6 patients receiving T cells with strong EBV reactivity showed clinical improvement, whereas only 1 of the 4 patients receiving T cells with weak EBV reactivity showed improvement (P = 0.033, Fisher's exact test). CONCLUSION: EBV-specific adoptive T cell therapy was well tolerated. Clinical improvement following treatment was associated with the potency of EBV-specific reactivity of the administered T cells. Further clinical trials are warranted to determine the efficacy of EBV-specific T cell therapy in MS. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12615000422527. FUNDING: MS Queensland, MS Research Australia, Perpetual Trustee Company Ltd., and donations from private individuals who wish to remain anonymous.

PREDICT-CP: study protocol of implementation of comprehensive surveillance to predict outcomes for school-aged children with cerebral palsy.

OBJECTIVES: Cerebral palsy (CP) remains the world's most common childhood physical disability with total annual costs of care and lost well-being of $A3.87b. The PREDICT-CP (NHMRC 1077257 Partnership Project: Comprehensive surveillance to PREDICT outcomes for school age children with CP) study will investigate the influence of brain structure, body composition, dietary intake, oropharyngeal function, habitual physical activity, musculoskeletal development (hip status, bone health) and muscle performance on motor attainment, cognition, executive function, communication, participation, quality of life and related health resource use costs. The PREDICT-CP cohort provides further follow-up at 8-12 years of two overlapping preschool-age cohorts examined from 1.5 to 5 years (NHMRC 465128 motor and brain development; NHMRC 569605 growth, nutrition and physical activity). METHODS AND ANALYSES: This population-based cohort study undertakes state-wide surveillance of 245 children with CP born in Queensland (birth years 2006-2009). Children will be classified for Gross Motor Function Classification System; Manual Ability Classification System, Communication Function Classification System and Eating and Drinking Ability Classification System. Outcomes include gross motor function, musculoskeletal development (hip displacement, spasticity, muscle contracture), upper limb function, communication difficulties, oropharyngeal dysphagia, dietary intake and body composition, participation, parent-reported and child-reported quality of life and medical and allied health resource use. These detailed phenotypical data will be compared with brain macrostructure and microstructure using 3 Tesla MRI (3T MRI). Relationships between brain lesion severity and outcomes will be analysed using multilevel mixed-effects models. ETHICS AND DISSEMINATION: The PREDICT-CP protocol is a prospectively registered and ethically accepted study protocol. The study combines data at 1.5-5 then 8-12 years of direct clinical assessment to enable prediction of outcomes and healthcare needs essential for tailoring interventions (eg, rehabilitation, orthopaedic surgery and nutritional supplements) and the projected healthcare utilisation. TRIAL REGISTRATION NUMBER: ACTRN: 12616001488493.

Midsagittal corpus callosum area and conversion to multiple sclerosis after clinically isolated syndrome: A multicentre Australian cohort study.

INTRODUCTION: Patients presenting with clinically isolated syndrome (CIS) may proceed to clinically definite multiple sclerosis (CDMS). Midsagittal corpus callosum area (CCA) is a surrogate marker for callosal atrophy, and can be obtained from a standard MRI study. This study explores the relationship between CCA measured at CIS presentation (baseline) and at 5 years post presentation, with conversion from CIS to CDMS. The association between CCA and markers of disability progression is explored. METHODS: Corpus callosum area was measured on MRI scans at presentation and 5-year review following diagnosis of a first demyelinating event, or evidence of progressive MS, in 143 participants in the Ausimmune/AusLong Study. Relationships between CCA (at baseline and follow-up) and clinical outcomes were assessed. RESULTS: Mean CCA at baseline study was 6.63 cm2 (SD 1.01). Patients who converted to MS by 5-year review (n = 100) had a significantly smaller mean CCA at follow-up (6.22 vs. 6.74, P = 0.007). Greater CCA reduction was associated with higher annualized relapse rate over follow-up. CONCLUSION: Baseline CCA obtained from standard MRI protocols may be compared with subsequent MRI examinations as a surrogate for neurodegeneration and cerebral atrophy in patients with MS. This study demonstrates an association between CCA and disability in individuals presenting with CIS who convert to MS.

Using the apparent diffusion coefficient to identifying MGMT promoter methylation status early in glioblastoma: importance of analytical method.

INTRODUCTION: Accurate knowledge of O(6)-methylguanine methyltransferase (MGMT) gene promoter subtype in patients with glioblastoma (GBM) is important for treatment. However, this test is not always available. Pre-operative diffusion MRI (dMRI) can be used to probe tumour biology using the apparent diffusion coefficient (ADC); however, its ability to act as a surrogate to predict MGMT status has shown mixed results. We investigated whether this was due to variations in the method used to analyse ADC. METHODS: We undertook a retrospective study of 32 patients with GBM who had MGMT status measured. Matching pre-operative MRI data were used to calculate the ADC within contrast enhancing regions of tumour. The relationship between ADC and MGMT was examined using two published ADC methods. RESULTS: A strong trend between a measure of 'minimum ADC' and methylation status was seen. An elevated minimum ADC was more likely in the methylated compared to the unmethylated MGMT group (U = 56, P = 0.0561). In contrast, utilising a two-mixture model histogram approach, a significant reduction in mean measure of the 'low ADC' component within the histogram was associated with an MGMT promoter methylation subtype (P < 0.0246). CONCLUSION: This study shows that within the same patient cohort, the method selected to analyse ADC measures has a significant bearing on the use of that metric as a surrogate marker of MGMT status. Thus for dMRI data to be clinically useful, consistent methods of data analysis need to be established prior to establishing any relationship with genetic or epigenetic profiling.

Validity of semi-quantitative scale for brain MRI in unilateral cerebral palsy due to periventricular white matter lesions: Relationship with hand sensorimotor function and structural connectivity.

AIM: To provide first evidence of construct validity of a semi-quantitative scale for brain structural MRI (sqMRI scale) in children with unilateral cerebral palsy (UCP) secondary to periventricular white matter (PWM) lesions, by examining the relationship with hand sensorimotor function and whole brain structural connectivity. METHODS: Cross-sectional study of 50 children with UCP due to PWM lesions using 3 T (MRI), diffusion MRI and assessment of hand sensorimotor function. We explored the relationship of lobar, hemispheric and global scores on the sqMRI scale, with fractional anisotropy (FA), as a measure of brain white matter microstructure, and with hand sensorimotor measures (Assisting Hand Assessment, AHA; Jebsen-Taylor Test for Hand Function, JTTHF; Melbourne Assessment of Unilateral Upper Limb Function, MUUL; stereognosis; 2-point discrimination). RESULTS: Lobar and hemispheric scores on the sqMRI scale contralateral to the clinical side of hemiplegia correlated with sensorimotor paretic hand function measures and FA of a number of brain structural connections, including connections of brain areas involved in motor control (postcentral, precentral and paracentral gyri in the parietal lobe). More severe lesions correlated with lower sensorimotor performance, with the posterior limb of internal capsule score being the strongest contributor to impaired hand function. CONCLUSION: The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure-function relationships but requires further validation in other populations of CP.

Magnetic resonance angiography or digital subtraction catheter angiography for follow-up of coiled aneurysms: do we need both?

INTRODUCTION: Endovascular treatment of intracranial aneurysms is now common. Digital subtraction catheter angiography (DSA) is the gold standard for imaging follow-up of coiled intracranial aneurysms; however, it is an invasive procedure with a risk of complications. Time-of-flight magnetic resonance angiography (MRA) is an alternative non-invasive imaging method. In a previous study, we found that MRA at 1.5T was comparable to DSA for detection of aneurysm recurrence in this patient group and subsequently added MRA to the routine follow-up protocol. In the current study, we further compare MRA with DSA to determine whether MRA could safely replace DSA. METHODS: Patients who had endovascular coiling procedure for intracranial aneurysm from 10/2004 to 6/2010 were identified from our database. A radiologist and a radiology registrar compared MRA and DSA for all patients who received both modalities. DSA was considered as the reference technique. 'Agreement' or 'disagreement' between modalities was noted regarding absence or presence of aneurysm recurrence. RESULTS: The study group comprised 86 treatments of 80 aneurysms in 73 patients. There were 83/86 agreements between modalities and 3 disagreements. In one case, MRA identified a recurrence that was not seen on the corresponding DSA. In two cases, DSA showed a minor recurrence that was not seen on MRA. CONCLUSION: Of the two MRA 'misses', neither would have resulted in different management. MRA is a safe and accurate modality for follow-up of coiled aneurysms and can replace DSA.

Carotid ultrasound pulsatility indices and cardiovascular risk in Australian women.

INTRODUCTION: Ultrasound-acquired internal carotid arterial (ICA) pulsatility indices (PI) have been demonstrated to be useful measures of cerebrovascular disease. The purpose of this cross-sectional study was to investigate the association between carotid artery PI, cardiovascular risk and ischaemic heart disease in aging women. METHODS: One hundred and fifty-eight female participants of the Longitudinal Assessment of Ageing in Women study, aged 48-85 years, were evaluated. The relationships between common carotid artery (CCA) and ICA Doppler PI to cardiovascular risk factors (age, body mass index, systolic and mean arterial blood pressure, smoking and diabetes), carotid-femoral (femPWV) and carotid-radial (radPWV) pulse wave velocities, and ischaemic heart disease (IHD) were assessed using Spearman's rank correlation (ρ), multiple regression and logistic regression. Dependent variables were Box-Cox transformed to meet linear regression assumptions. RESULTS: CCA and ICA PI were significantly correlated to femPWV (ρ = 0.414 and ρ = 0.544, respectively). Cardiovascular risk factors were significantly predictive of CCA PI (Adj R(2) = 0.176, P < 0.01); however, their relationship to ICA PI (Adj R(2) = 0.508, P < 0.01) was stronger. This result was comparable with the relationship between cardiovascular risk factors and femPWV (Adj R(2) = 0.561, P < 0.01). Age and systolic blood pressure were the dominant risk factors for IHD in this group. CONCLUSION: ICA PI is comparable with femPWV in its association with cardiovascular disease. PI does not improve the prediction of IHD over age and systolic blood pressure.

Epstein-Barr virus-specific adoptive immunotherapy for progressive multiple sclerosis.

Defective control of Epstein-Barr virus (EBV) infection by cytotoxic CD8(+) T cells might predispose to multiple sclerosis (MS) by allowing EBV-infected autoreactive B cells to accumulate in the central nervous system. We have treated a patient with secondary progressive MS with in vitro-expanded autologous EBV-specific CD8(+) T cells directed against viral latent proteins. This adoptive immunotherapy had no adverse effects and the patient showed clinical improvement with reduced disease activity on magnetic resonance imaging and decreased intrathecal immunoglobulin production. This is the first report of the use of EBV-specific adoptive immunotherapy to treat MS or any other autoimmune disease.

Distance informed Track-Weighted Imaging (diTWI): a framework for sensitising streamline information to neuropathology.

Track-Weighted Imaging (TWI), where voxel intensity is based on image metrics encoded along streamline trajectories, provides a mechanism to study white matter disease. However, with generalised streamline weighting, it is difficult to localise the precise anatomical source and spread of injury or neuropathology. This limitation can be overcome by modulating the voxel weight based on the distance of the voxel from a given anatomical location along the tract, which we term diTWI: distance informed Track-Weighted Imaging. The location of known neuropathology can be delineated on any given imaging modality (e.g. MRI or PET). To demonstrate the clinical utility of this approach, we measured tumour cell infiltration along WM fibre tracts in 13 patients with newly diagnosed glioblastoma and 1 patient with Anaplastic Astrocytoma. TWI and diTWI maps were generated using information obtained from dynamic contrast enhanced MRI (area under the curve, AUC) and diffusivity maps (ADC and FA) with tumour boundaries automatically extracted using a logistic regression classifier. The accuracy of the derived tumour volumes was compared to those generated using 3,4-dihydroxy-6-[(18)F]-fluoro-l-phenylalanine (FDOPA) PET imaging. The accuracy of the tumour volumes generated from the diTWI maps was superior to volumes derived from the TWI, geometric distance or baseline AUC, FA and ADC maps. The relative overlap and relative dissimilarity rates for the diTWI generated tumour volumes after classification were found to be 82.3±15.3% (range 69.1-91.9) and 16.9±8.8% (range 7.9-37.5), respectively. These findings show that diTWI maps provide a useful framework for localising neuropathological processes occurring along WM pathways.

Magnetic resonance imaging: an accurate, radiation-free, alternative to computed tomography for the primary imaging and three-dimensional reconstruction of the bony orbit.

PURPOSE: To determine the extent to which the accuracy of magnetic resonance imaging (MRI) based virtual 3-dimensional (3D) models of the intact orbit can approach that of the gold standard, computed tomography (CT) based models. The goal was to determine whether MRI is a viable alternative to CT scans in patients with isolated orbital fractures and penetrating eye injuries, pediatric patients, and patients requiring multiple scans in whom radiation exposure is ideally limited. MATERIALS AND METHODS: Patients who presented with unilateral orbital fractures to the Royal Brisbane and Women's Hospital from March 2011 to March 2012 were recruited to participate in this cross-sectional study. The primary predictor variable was the imaging technique (MRI vs CT). The outcome measurements were orbital volume (primary outcome) and geometric intraorbital surface deviations (secondary outcome) between the MRI- and CT-based 3D models. RESULTS: Eleven subjects (9 male) were enrolled. The patients' mean age was 30 years. On average, the MRI models underestimated the orbital volume of the CT models by 0.50 ± 0.19 cm(3). The average intraorbital surface deviation between the MRI and CT models was 0.34 ± 0.32 mm, with 78 ± 2.7% of the surface within a tolerance of ±0.5 mm. CONCLUSIONS: The volumetric differences of the MRI models are comparable to reported results from CT models. The intraorbital MRI surface deviations are smaller than the accepted tolerance for orbital surgical reconstructions. Therefore, the authors believe that MRI is an accurate radiation-free alternative to CT for the primary imaging and 3D reconstruction of the bony orbit.

The physical anthropometry, lifestyle habits and blood pressure of people presenting with a first clinical demyelinating event compared to controls: the Ausimmune study.

INTRODUCTION: Lifestyle factors prior to a first clinical demyelinating event (FCD), a disorder often preceding the development of clinically definite multiple sclerosis (MS), have not previously been examined in detail. Past tobacco smoking has been consistently associated with MS. METHODS: This was a multicentre incident case-control study. Cases (n = 282) were aged 18-59 years with an FCD and resident within one of four Australian centres (from latitudes 27°S to 43°S), from 1 November 2003 to 31 December 2006. Controls (n = 558) were matched to cases on age, sex and study region, without CNS demyelination. Exposures measured included current and past tobacco and marijuana, alcohol and beverage use, physical activity patterns, blood pressure and physical anthropometry. RESULTS: A history of smoking ever was associated with FCD risk (AOR 1.89 (95%CL 1.82, 3.52)). Marijuana use was not associated with FCD risk after adjusting for confounders such as smoking ever but the estimates were imprecise because of a low prevalence of use. Alcohol consumption was common and not associated with FCD risk. No case-control differences in blood pressure or physical anthropometry were observed. CONCLUSIONS: Past tobacco smoking was positively associated with a risk of FCD but most other lifestyle factors were not. Prevention efforts against type 2 diabetes and cardiovascular disease by increasing physical activity and reducing obesity are unlikely to alter MS incidence, and more targeted campaigns will be required.

Imaging and diagnostic criteria for Multiple Sclerosis: are we there yet?

INTRODUCTION: Excluding post traumatic injury, Multiple Sclerosis (MS) is the most common disabling neurological disorder of young adults. Although the effect on mortality is limited, the association of a young demographic and significant morbidity combine to make MS a devastating disease. Since MS was given its first detailed description in 1868, diagnostic criteria continue to evolve. Recently, there has been an international commitment to combine both clinical and paraclinical tests to arrive at an earlier diagnosis. Widespread acceptance of the use of MRI in diagnosis, monitoring and research has made the role of the radiologist more critical than ever in this disease. The primary diagnostic criteria for MS are the International Panel criteria, commonly referred to as the McDonald criteria and it is essential that the radiology community is aware of the work preceding these criteria, so that they are understood in the correct context and the importance acknowledged. METHODS: Literature review utilising key word search to obtain the historical and current context of magnetic resonance imaging in the diagnosis of MS. RESULTS: A succinct description of the evolution of criteria for the diagnosis of MS. CONCLUSIONS: Radiologists must recognise that there are specific diagnostic criteria for MS that continue to evolve as a result of new research, improved technology and clinical experience and it is crucial that these criteria be applied in daily practice. It should be evident that diagnostic imaging criteria for MS will be most effective when combined with standardised MRI protocols such as those published by the international Consortium of Multiple Sclerosis Centres.

Adherence to MRI protocol consensus guidelines in multiple sclerosis: an Australian multi-centre study.

INTRODUCTION: Multiple sclerosis (MS) is a debilitating disease that causes significant morbidity within a young demographic. Diagnostic guidelines for MS have evolved, and imaging has played an increasingly important role in diagnosis over the last two decades. For imaging to contribute to diagnosis in a meaningful way, it must be reproducible. Consensus guidelines for MRI in MS exist to define correct sequence type and imaging technique, but it is not clear to what extent they are followed. This study reviewed MRI studies performed on Australian individuals presenting with a first clinical diagnosis of central nervous system demyelination (FCD) for adherence to published guidelines and discussed practical implementation of MS guidelines in light of recent updates. METHODS: The Ausimmune study was a prospective case control study of Australian participants presenting with FCD from 2003 to 2006. Baseline cranial and spinal cord MRI studies of 226 case participants from four separate Australian regions were reviewed. MRI sequences were classified according to anatomical location, slice plane, tissue weighting and use of gadolinium-containing contrast media. Results were compared with the 2003 Consortium of Multiple Sclerosis Centres MRI protocol for the diagnosis of MS. RESULTS: The composition of core cranial MRI sequences performed varied across the 226 scans. Of the studies, 91% included sagittal fluid attenuated inversion recovery (FLAIR) sequences. Cranial axial T2-weighted, axial FLAIR and axial proton density-weighted sequences were performed in 88%, 60% and 16% (respectively) of scans. Only 25% of the studies included a T1-weighted contrast-enhanced sequence. Concordance with the guidelines in all sequences was very low (2). CONCLUSION: Only a small number of MRI investigations performed included all of the sequences stipulated by consensus guidelines. This is likely due to poor awareness in the imaging community of the guidelines and the rationale behind certain sequences. Radiologists with a sub-speciality interest in neuroradiology should take ownership of this issue and ensure that recommended imaging guidelines are followed.