The impact of the Covid-19 pandemic on adult diagnostic neuroradiology in Europe.

PURPOSE: The purpose of this survey was to understand the impact the Covid-19 pandemic has or has had on the work, training, and wellbeing of professionals in the field of diagnostic neuroradiology. METHODS: A survey was emailed to all ESNR members and associates as well as distributed via professional social media channels. The survey was held in the summer of 2020 when the first wave had subsided in most of Europe, while the second wave was not yet widespread. The questionnaire featured a total of 46 questions on general demographics, the various phases of the healthcare crisis, and the numbers of Covid-19 patients. RESULTS: One hundred sixty-seven responses were received from 48 countries mostly from neuroradiologists (72%). Most commonly taken measures during the crisis phase were reduction of outpatient exams (87%), reduction of number of staff present in the department (83%), reporting from home (62%), and shift work (54%). In the exit phase, these measures were less frequently applied, but reporting from home was still frequent (33%). However, only 22% had access to a fully equipped work station at home. While 81% felt safe at work during the crisis, fewer than 50% had sufficient personal protection equipment for the duration of the entire crisis. Mental wellbeing is an area of concern, with 61% feeling (much) worse than usual. Many followed online courses/congresses and considered these a viable alternative for the future. CONCLUSION: The Covid-19 pandemic substantially affected the professional life as well as personal wellbeing of neuroradiologists.

FLAIR-only joint volumetric analysis of brain lesions and atrophy in clinically isolated syndrome (CIS) suggestive of multiple sclerosis.

BACKGROUND: MRI assessment in multiple sclerosis (MS) focuses on the presence of typical white matter (WM) lesions. Neurodegeneration characterised by brain atrophy is recognised in the research field as an important prognostic factor. It is not routinely reported clinically, in part due to difficulty in achieving reproducible measurements. Automated MRI quantification of WM lesions and brain volume could provide important clinical monitoring data. In general, lesion quantification relies on both T1 and FLAIR input images, while tissue volumetry relies on T1. However, T1-weighted scans are not routinely included in the clinical MS protocol, limiting the utility of automated quantification. OBJECTIVES: We address an aspect of this important translational challenge by assessing the performance of FLAIR-only lesion and brain segmentation, against a conventional approach requiring multi-contrast acquisition. We explore whether FLAIR-only grey matter (GM) segmentation yields more variability in performance compared with two-channel segmentation; whether this is related to field strength; and whether the results meet a level of clinical acceptability demonstrated by the ability to reproduce established biological associations. METHODS: We used a multicentre dataset of subjects with a CIS suggestive of MS scanned at 1.5T and 3T in the same week. WM lesions were manually segmented by two raters, 'manual 1' guided by consensus reading of CIS-specific lesions and 'manual 2' by any WM hyperintensity. An existing brain segmentation method was adapted for FLAIR-only input. Automated segmentation of WM hyperintensity and brain volumes were performed with conventional (T1/T1 + FLAIR) and FLAIR-only methods. RESULTS: WM lesion volumes were comparable at 1.5T between 'manual 2' and FLAIR-only methods and at 3T between 'manual 2', T1 + FLAIR and FLAIR-only methods. For cortical GM volume, linear regression measures between conventional and FLAIR-only segmentation were high (1.5T: α = 1.029, R2 = 0.997, standard error (SE) = 0.007; 3T: α = 1.019, R2 = 0.998, SE = 0.006). Age-associated change in cortical GM volume was a significant covariate in both T1 (p = 0.001) and FLAIR-only (p = 0.005) methods, confirming the expected relationship between age and GM volume for FLAIR-only segmentations. CONCLUSIONS: FLAIR-only automated segmentation of WM lesions and brain volumes were consistent with results obtained through conventional methods and had the ability to demonstrate biological effects in our study population. Imaging protocol harmonisation and validation with other MS phenotypes could facilitate the integration of automated WM lesion volume and brain atrophy analysis as clinical tools in radiological MS reporting.

Dementia imaging in clinical practice: a European-wide survey of 193 centres and conclusions by the ESNR working group.

PURPOSE: Through a European-wide survey, we assessed the current clinical practice of imaging in the primary evaluation of dementia, with respect to standardised imaging, evaluation and reporting. METHODS: An online questionnaire was emailed to all European Society of Neuroradiology (ESNR) members (n = 1662) and non-members who had expressed their interest in ESNR activities in the past (n = 6400). The questionnaire featured 42 individual items, divided into multiple choice, single best choice and free text answers. Information was gathered on the context of the practices, available and preferred imaging modalities, applied imaging protocols and standards for interpretation, reporting and communication. RESULTS: A total of 193 unique (non-duplicate) entries from the European academic and non-academic institutions were received from a total of 28 countries. Of these, 75% were neuroradiologists, 12% general radiologists and 11% (neuro) radiologists in training. Of responding centres, 38% performed more than five scans/week for suspected dementia. MRI was primarily used in 72% of centres. Over 90% of centres acquired a combination of T2w, FLAIR, T1w, DWI and T2*w sequences. Visual rating scales were used in 75% of centres, most often the Fazekas and medial temporal atrophy scale; 32% of respondents lacked full confidence in their use. Only 23% of centres performed volumetric analysis. A minority of centres (28%) used structured reports. CONCLUSIONS: Current practice in dementia imaging is fairly homogeneous across Europe, in terms of image acquisition and image interpretation. Hurdles identified include training on the use of visual rating scales, implementation of volumetric assessment and structured reporting.

Apparent diffusion coefficient for molecular subtyping of non-gadolinium-enhancing WHO grade II/III glioma: volumetric segmentation versus two-dimensional region of interest analysis.

OBJECTIVES: To investigate if quantitative apparent diffusion coefficient (ADC) measurements can predict genetic subtypes of non-gadolinium-enhancing gliomas, comparing whole tumour against single slice analysis. METHODS: Volumetric T2-derived masks of 44 gliomas were co-registered to ADC maps with ADC mean (ADCmean) calculated. For the slice analysis, two observers placed regions of interest in the largest tumour cross-section. The ratio (ADCratio) between ADCmean in the tumour and normal appearing white matter was calculated for both methods. RESULTS: Isocitrate dehydrogenase (IDH) wild-type gliomas showed the lowest ADC values throughout (p < 0.001). ADCmean in the IDH-mutant 1p19q intact group was significantly higher than in the IDH-mutant 1p19q co-deleted group (p < 0.01). A volumetric ADCmean threshold of 1201 × 10-6 mm2/s identified IDH wild-type with a sensitivity of 83% and a specificity of 86%; a volumetric ADCratio cut-off value of 1.65 provided a sensitivity of 80% and a specificity of 92% (area under the curve (AUC) 0.9-0.94). A slice ADCratio threshold for observer 1 (observer 2) of 1.76 (1.83) provided a sensitivity of 80% (86%), specificity of 91% (100%) and AUC of 0.95 (0.96). The intraclass correlation coefficient was excellent (0.98). CONCLUSIONS: ADC measurements can support the distinction of glioma subtypes. Volumetric and two-dimensional measurements yielded similar results in this study. KEY POINTS: • Diffusion-weighted MRI aids the identification of non-gadolinium-enhancing malignant gliomas • ADC measurements may permit non-gadolinium-enhancing glioma molecular subtyping • IDH wild-type gliomas have lower ADC values than IDH-mutant tumours • Single cross-section and volumetric ADC measurements yielded comparable results in this study.

9.4 T MR microscopy of the substantia nigra with pathological validation in controls and disease.

BACKGROUND: The anatomy of the substantia nigra on conventional MRI is controversial. Even using histological techniques it is difficult to delineate with certainty from surrounding structures. We sought to define the anatomy of the SN using high field spin-echo MRI of pathological material in which we could study the anatomy in detail to corroborate our MRI findings in controls and Parkinson's disease and progressive supranuclear palsy. METHODS: 23 brains were selected from the Queen Square Brain Bank (10 controls, 8 progressive supranuclear palsy, 5 Parkinson's disease) and imaged using high field 9.4 Tesla spin-echo MRI. Subsequently brains were cut and stained with Luxol fast blue, Perls stain, and immunohistochemistry for substance P and calbindin. Once the anatomy was defined on histology the dimensions and volume of the substantia nigra were determined on high field magnetic resonance images. RESULTS: The anterior border of the substantia nigra was defined by the crus cerebri. In the medial half it was less distinct due to the deposition of iron and the interdigitation of white matter and the substantia nigra. The posterior border was flanked by white matter bridging the red nucleus and substantia nigra and seen as hypointense on spin-echo magnetic resonance images. Within the substantia nigra high signal structures corresponded to confirmed nigrosomes. These were still evident in Parkinson's disease but not in progressive supranuclear palsy. The volume and dimensions of the substantia nigra were similar in Parkinson's disease and controls, but reduced in progressive supranuclear palsy. CONCLUSIONS: We present a histologically validated anatomical description of the substantia nigra on high field spin-echo high resolution magnetic resonance images and were able to delineate all five nigrosomes. In accordance with the pathological literature we did not observe changes in the nigrosome structure as manifest by volume or signal characteristics within the substantia nigra in Parkinson's disease whereas in progressive supranuclear palsy there was microarchitectural destruction.

Hippocampal and Deep Gray Matter Nuclei Atrophy Is Relevant for Explaining Cognitive Impairment in MS: A Multicenter Study.

BACKGROUND AND PURPOSE: The structural MR imaging correlates of cognitive impairment in multiple sclerosis are still debated. This study assessed lesional and atrophy measures of white matter and gray matter involvement in patients with MS acquired in 7 European sites to identify the MR imaging variables most closely associated with cognitive dysfunction. MATERIALS AND METHODS: Brain dual-echo, 3D T1-weighted, and double inversion recovery scans were acquired at 3T from 62 patients with relapsing-remitting MS and 65 controls. Patients with at least 2 neuropsychological tests with abnormal findings were considered cognitively impaired. Focal WM and cortical lesions were identified, and volumetric measures from WM, cortical GM, the hippocampus, and deep GM nuclei were obtained. Age- and site-adjusted models were used to compare lesion and volumetric MR imaging variables between patients with MS who were cognitively impaired and cognitively preserved. A multivariate analysis identified MR imaging variables associated with cognitive scores and disability. RESULTS: Twenty-three patients (38%) were cognitively impaired. Compared with those with who were cognitively preserved, patients with MS with cognitive impairment had higher T2 and T1 lesion volumes and a trend toward a higher number of cortical lesions. Significant brain, cortical GM, hippocampal, deep GM nuclei, and WM atrophy was found in patients with MS with cognitive impairment versus those who were cognitively preserved. Hippocampal and deep GM nuclei atrophy were the best predictors of cognitive impairment, while WM atrophy was the best predictor of disability. CONCLUSIONS: Hippocampal and deep GM nuclei atrophy are key factors associated with cognitive impairment in MS. These MR imaging measures could be applied in a multicenter context, with cognition as clinical outcome.

Multiparameter MR imaging in the 6-OPRI variant of inherited prion disease.

BACKGROUND AND PURPOSE: Inherited prion diseases represent over 15% of human prion cases and are a frequent cause of early onset dementia. The purpose of this study was to define the distribution of changes in cerebral volumetric and microstructural parenchymal tissues in a specific inherited human prion disease mutation combining VBM with VBA of cerebral MTR and MD. MATERIALS AND METHODS: VBM and VBA of cerebral MTR and MD were performed in 16 healthy control participants and 9 patients with the 6-OPRI mutation. An analysis of covariance consisting of diagnostic grouping with age and total intracranial volume as covariates was performed. RESULTS: On VBM, there was a significant reduction in gray matter volume in patients compared with control participants in the basal ganglia, perisylvian cortex, lingual gyrus, and precuneus. Significant MTR reduction and MD increases were more anatomically extensive than volume differences on VBM in the same cortical areas, but MTR and MD changes were not seen in the basal ganglia. CONCLUSIONS: Gray matter and WM changes were seen in brain areas associated with motor and cognitive functions known to be impaired in patients with the 6-OPRI mutation. There were some differences in the anatomic distribution of MTR-VBA and MD-VBA changes compared with VBM, likely to reflect regional variations in the type and degree of the respective pathophysiologic substrates. Combined analysis of complementary multiparameter MR imaging data furthers our understanding of prion disease pathophysiology.

Skeletal muscle MRI magnetisation transfer ratio reflects clinical severity in peripheral neuropathies.

MRI may provide treatment outcome measures in neuromuscular conditions. The authors assessed MRI magnetisation transfer ratios (MTRs) in lower-limb musculature as markers of pathology in peripheral neuropathies and compared the findings with associated clinical data. Ten patients with Charcot-Marie-Tooth disease type 1A (CMT1A) and nine patients with chronic inflammatory demyelinating polyneuropathy (CIDP) were compared with 10 healthy subjects. The MTR in the calf muscles was significantly lower than controls in the two patient groups (both p<0.001). The median MTRs (IQR) were 50.5(1.6) percentage units (p.u.) (control), 41.5(10.6) p.u. (CMT1A) and 39.3(8.7) p.u. (CIDP). Moreover, anterior lower leg MTR correlated strongly with strength of ankle dorsiflexion, measured with the Medical Research Council scale, in CIDP (ρ=0.88, p<0.001) and also in CMT1A (ρ=0.50, p<0.05), where MTR also showed an association with disease duration (ρ=-0.86, p<0.001). Short tau inversion recovery MRI of the same muscles showed abnormalities associated with regions of reduced MTR (p<0.001), and MTR was also reduced in other muscles otherwise deemed normal appearing (p<0.001), indicating that MTR may be more sensitive to muscle damaged by denervation than conventional MRI. The significant reductions in muscle MTR in peripheral neuropathies and the associated correlations with clinical measures indicate that MTR has potential as an imaging outcome measure in future therapeutic trials.

Correcting radiofrequency inhomogeneity effects in skeletal muscle magnetisation transfer maps.

The potential of MRI to provide quantitative measures of neuromuscular pathology for use in therapeutic trials is being increasingly recognised. Magnetisation transfer (MT) imaging shows particular promise in this context, being sensitive to pathological changes, particularly in skeletal muscle, where measurements correlate with clinically measured muscle strength. Radiofrequency (RF) transmit field (B(1)) inhomogeneities can be particularly problematic in measurements of the MT ratio (MTR) and may obscure genuine muscle MTR changes caused by disease. In this work, we evaluate, for muscle imaging applications, a scheme previously proposed for the correction of RF inhomogeneity artefacts in cerebral MTR maps using B(1) information acquired in the same session. We demonstrate the theoretical applicability of this scheme to skeletal muscle using a two-pool model of pulsed quantitative MT. The correction scheme is evaluated practically in MTR imaging of the lower limbs of 28 healthy individuals and in two groups of patients with representative neuromuscular diseases: Charcot-Marie-Tooth disease type 1A and inclusion body myositis. The correction scheme was observed to reduce both the within-subject and between-subject variability in the calf and thigh muscles of healthy subjects and patient groups in histogram- and region-of-interest-based approaches. This method of correcting for RF inhomogeneity effects in MTR maps using B(1) data may markedly improve the sensitivity of MTR mapping indices as measures of pathology in skeletal muscle.

High resolution MR anatomy of the subthalamic nucleus: imaging at 9.4 T with histological validation.

Using conventional MRI the subthalamic nucleus (STN) is not clearly defined. Our objective was to define the anatomy of the STN using 9.4 T MRI of post mortem tissue with histological validation. Spin-echo (SE) and 3D gradient-echo (GE) images were obtained at 9.4 T in 8 post mortem tissue blocks and compared directly with corresponding histological slides prepared with Luxol Fast Blue/Cresyl Violet (LFB/CV) in 4 cases and Perl stain in 3. The variability of the STN anatomy was studied using internal reference points. The anatomy of the STN and surrounding structures was demonstrated in all three anatomical planes using 9.4 T MR images in concordance with LFB/CV stained histological sections. Signal hypointensity was seen in 6/8 cases in the anterior and medial STN that corresponded with regions of more intense Perl staining. There was significant variability in the volume, shape and location of the borders of the STN. Using 9.4 T MRI, the internal signal characteristics and borders of the STN are clearly defined and significant anatomical variability is apparent. Direct visualisation of the STN is possible using high field MRI and this is particularly relevant, given its anatomical variability, for planning deep brain stimulation.

Consensus recommendations for MS cortical lesion scoring using double inversion recovery MRI.

BACKGROUND: Different double inversion recovery (DIR) sequences are currently used in multiple sclerosis (MS) research centers to visualize cortical lesions, making it difficult to compare published data. This study aimed to formulate consensus recommendations for scoring cortical lesions in patients with MS, using DIR images acquired in 6 European centers according to local protocols. METHODS: Consensus recommendations were formulated and tested in a multinational meeting. RESULTS: Cortical lesions were defined as focal abnormalities on DIR, hyperintense compared to adjacent normal-appearing gray matter, and were not scored unless ≥ 3 pixels in size, based on at least 1.0 mm(2) in-plane resolution. Besides these 2 obligatory criteria, additional, supportive recommendations concerned a priori artifact definition on DIR, use of additional MRI contrasts to verify suspected lesions, and a constant level of displayed image contrast. Robustness of the recommendations was tested in a small dataset of available, heterogeneous DIR images, provided by the different participating centers. An overall moderate agreement was reached when using the proposed recommendations: more than half of the readers agreed on slightly more than half (54%) of the cortical lesions scored, whereas complete agreement was reached in 19.4% of the lesions (usually larger, mixed white matter/gray matter lesions). CONCLUSIONS: Although not designed as a formal interobserver study, the current study suggests that comparing available literature data on cortical lesions may be problematic, and increased consistency in acquisition protocols may improve scoring agreement. Sensitivity and specificity of the proposed recommendations should now be studied in a more formal, prospective, multicenter setting using similar DIR protocols.

BG-12 reduces evolution of new enhancing lesions to T1-hypointense lesions in patients with multiple sclerosis.

BG-12, an immunomodulatory agent, reduces frequency of new gadolinium-enhancing (Gd+) lesions in relapsing multiple sclerosis (MS). This study reports the effect of 240 mg BG-12 orally three times daily (tid) for 24 weeks on the evolution of new Gd+ lesions to T1-hypointense lesions. Brain magnetic resonance imaging (MRI) scans from patients in placebo and 240 mg BG-12 tid arms of a phase 2b study were examined retrospectively. Included patients had at least one new Gd+ lesion from weeks 4 to 12. Week 24 scans were analyzed for number and proportion of new Gd+ lesions that evolved to T1-hypointense lesions. Eighteen patients receiving BG-12 and 38 patients receiving placebo were included in the analysis. The analysis tracked 147 new Gd+ lesions in patients from the BG-12 group and 221 Gd+ lesions in patients from the placebo group. The percentage of Gd+ lesions that evolved to T1-hypointense lesions was 34% lower with BG-12 treatment versus placebo (29%, BG-12; 44%, placebo; odds ratio 0.51; 95% confidence interval 0.43, 0.61; p < 0.0001). In addition to reducing frequency of new Gd+ lesions, BG-12 significantly reduced probability of their evolution to T1-hypointense lesions in patients with MS compared with placebo.

MRI shows increased sciatic nerve cross sectional area in inherited and inflammatory neuropathies.

Measurements of the cross sectional area of the sciatic nerve are described in a group of 10 patients with genetically confirmed Charcot-Marie-Tooth disease type 1A (CMT1A), nine patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and 10 healthy controls using MRI. One mid-thigh of each individual was imaged using a short tau inversion recovery sequence and the nerve appearance evaluated radiologically with respect to the signal intensity and visibility of the internal neural structure. The cross sectional area of the sciatic nerve of each individual was measured by defining irregular enclosing regions of interest on the MRI images. The sciatic nerve area was enlarged in both CMT1A (p<0.001) and CIDP (p=0.008) compared with controls and in CMT1A compared with CIDP (p<0.001). Median (interquartile range) areas were 67.6 (16.2) mm(2) for the CIDP group, 135.9 (46.5) mm(2) for the CMT1A group and 43.3 (19.9) mm(2) for the control group. The critical upper value for discriminating pathologically enlarged nerves from normal controls with p<0.05 was 64.4 mm(2). Quantification of sciatic nerve hypertrophy on MRI may be of assistance in cases where the diagnosis is still in doubt, providing an objective pathological marker complimenting other clinical investigations.

Brain microbleeds as a potential risk factor for antiplatelet-related intracerebral haemorrhage: hospital-based, case-control study.

BACKGROUND: Intracerebral haemorrhage (ICH) is an uncommon but devastating complication of regular antiplatelet use: identifying high-risk patients before treatment could potentially reduce this hazard. Brain microbleeds on gradient-recalled echo (GRE) T2*-weighted MRI are considered a biomarker for bleeding-prone small-vessel diseases. The authors hypothesised that microbleeds are a risk factor for antiplatelet-related ICH, and investigated this in a hospital-based matched case-control study. METHODS: Cases of spontaneous ICH were ascertained, using overlapping methods, from a prospective database of 1017 consecutive unselected patients referred to our stroke unit and associated clinics. For each case of antiplatelet-related ICH, two controls matched for age, sex and hypertension without history of ICH on antiplatelet therapy were selected. Microbleeds were identified by a trained observer blinded to clinical details. RESULTS: Microbleeds were more frequent in antiplatelet users with ICH than in matched antiplatelet users without ICH (13/16 (81%) vs 6/32 (19%), p=0.004) and patients with non-antiplatelet-related ICH (13/16 (81%) vs 15/33 (45%), p=0.03). The frequency of lobar microbleeds was 11/16 (69%) in antiplatelet-related ICH versus 11/33 (33%) in non antiplatelet-related ICH (p=0.032). Microbleeds were more numerous in antiplatelet users with ICH compared with controls (p=0.016). The number of microbleeds was associated with the risk of antiplatelet-related ICH (adjusted OR 1.33 per additional microbleed, 95% CI 1.06 to 1.66, p=0.013). CONCLUSIONS: Brain microbleeds are associated with antiplatelet-related ICH. In patients with a large number of lobar microbleeds, the risk of ICH could outweigh the benefits of antiplatelet therapy. Larger prospective studies to investigate the prognostic significance of microbleeds in regular antiplatelet users are warranted.

Anatomy of the substantia nigra and subthalamic nucleus on MR imaging.

The substantia nigra and subthalamic nucleus are two key structures in the midbrain that are very important in movement disorders, particularly those associated with parkinsonism. Using conventional magnetic resonance (MR) imaging, the anatomic description of both these structures can be challenging. This article describes the importance of understanding the underlying anatomy and some of the changes associated with pathology in these structures. Advances in MR imaging are discussed, including high-field MR imaging, diffusion tensor imaging, inversion-recovery imaging, and susceptibility-weighted imaging, with particular reference to the substantia nigra and subthalamic nucleus. Understanding of MR imaging features of these nuclei needs to be firmly based on underlying knowledge of anatomy and pathology from postmortem studies, and more work is needed in this field.

High-b-value diffusion MR imaging and basal nuclei apparent diffusion coefficient measurements in variant and sporadic Creutzfeldt-Jakob disease.

BACKGROUND AND PURPOSE: DWI using a standard b-value of 1000 s/mm(2) has emerged as the most sensitive sequence for the diagnosis of CJD. The purpose of this study was to investigate whether DWI at a high b-value (b = 3000 s/mm(2)) and ADC measurements in the basal nuclei improve the diagnosis of vCJD and sCJD compared with visual assessment of DWI at a standard b-value (b = 1000 s/mm(2)). MATERIALS AND METHODS: Eight patients with vCJD, 9 patients with sCJD, and 5 healthy volunteers underwent DWI at b = 1000 s/mm(2), and 5 vCJD patients, 4 sCJD patients, and 1 growth hormone-related CJD patient underwent DWI at b = 3000 s/mm(2). Two consultant neuroradiologists performed a visual comparison of the b = 1000 and b = 3000 images. Mean MR SI and ADC values were determined for C, P, and DM thalamus ROIs bilaterally at each b-value. SI ratios for each ROI relative to white matter were calculated. RESULTS: In 9 out of 10 patients, the higher b-value images were more sensitive to SI change, particularly in cortex and thalamus, with higher SI ratios at b = 3000 in the DM thalamus. For sCJD at b = 1000, we found significantly lower ADC values in the C and P compared with controls (mean C ADC = 587.3 +/- 84.7 mm(2)/s in sCJD patients versus 722.7 +/- 16.6 mm(2)/s in controls; P = .007), and at b = 3000, the differences were more pronounced. In comparison, in vCJD at b = 1000, ADC values were elevated in the Pu (mean Pu ADC = 837.6 +/- 33.0 mm/s(2) in vCJD patients versus 748.0 +/- 17.3 mm/s(2) in controls; P < .001) but failed to reach significance at b = 3000. CONCLUSIONS: Our results demonstrate that b = 3000 DWI, being more sensitive to slowly diffusing tissue water, is more sensitive to pathology in sCJD than is conventional DWI. High-b-value DWI increases confidence in the radiologic diagnosis of human prion disease.

The Microbleed Anatomical Rating Scale (MARS): reliability of a tool to map brain microbleeds.

OBJECTIVE: Brain microbleeds on gradient-recalled echo (GRE) T2*-weighted MRI may be a useful biomarker for bleeding-prone small vessel diseases, with potential relevance for diagnosis, prognosis (especially for antithrombotic-related bleeding risk), and understanding mechanisms of symptoms, including cognitive impairment. To address these questions, it is necessary to reliably measure their presence and distribution in the brain. We designed and systematically validated the Microbleed Anatomical Rating Scale (MARS). We measured intrarater and interrater agreement for presence, number, and anatomical distribution of microbleeds using MARS across different MRI sequences and levels of observer experience. METHODS: We studied a population of 301 unselected consecutive patients admitted to our stroke unit using 2 GRE T2*-weighted MRI sequences (echo time [TE] 40 and 26 ms). Two independent raters with different MRI rating expertise identified, counted, and anatomically categorized microbleeds. RESULTS: At TE = 40 ms, agreement for microbleed presence in any brain location was good to very good (intrarater kappa = 0.85 [95% confidence interval (CI) 0.77-0.93]; interrater kappa = 0.68 [95% CI 0.58-0.78]). Good to very good agreement was reached for the presence of microbleeds in each anatomical region and in individual cerebral lobes. Intrarater and interrater reliability for the number of microbleeds was excellent (intraclass correlation coefficient [ICC] = 0.98 [95% CI 0.97-0.99] and ICC = 0.93 [0.91-0.94]). Very good interrater reliability was obtained at TE = 26 ms (kappa = 0.87 [95% CI 0.61-1]) for definite microbleeds in any location. CONCLUSION: The Microbleed Anatomical Rating Scale has good intrarater and interrater reliability for the presence of definite microbleeds in all brain locations when applied to different MRI sequences and levels of observer experience.

MRI features of benign multiple sclerosis: toward a new definition of this disease phenotype.

It is well known that the current classification of patients with benign multiple sclerosis (BMS), i.e., those with absent or minimal locomotor disability several years after disease onset, suffers from not having any prognostic value for the subsequent evolution of multiple sclerosis (MS). The identification of markers predictive of the longer-term course of MS will help define BMS more reliably and would allow better counseling of patients, particularly when advising on the initiation of a disease-modifying treatment. MRI-based evidence suggests that there are three potential, but not mutually exclusive, explanations for the scarce clinical impact of BMS: 1) the paucity of tissue damage within and outside MS lesions; 2) the relative sparing of clinically eloquent regions; and 3) the presence of effective compensatory mechanisms. In addition, the results of correlative MRI/neuropsychology studies underpin the need for a new definition of BMS, which should consider the maintenance of a normal cognitive profile as an additional criterion.

Sample sizes for brain atrophy outcomes in trials for secondary progressive multiple sclerosis.

BACKGROUND: Progressive brain atrophy in multiple sclerosis (MS) may reflect neuroaxonal and myelin loss and MRI measures of brain tissue loss are used as outcome measures in MS treatment trials. This study investigated sample sizes required to demonstrate reduction of brain atrophy using three outcome measures in a parallel group, placebo-controlled trial for secondary progressive MS (SPMS). METHODS: Data were taken from a cohort of 43 patients with SPMS who had been followed up with 6-monthly T1-weighted MRI for up to 3 years within the placebo arm of a therapeutic trial. Central cerebral volumes (CCVs) were measured using a semiautomated segmentation approach, and brain volume normalized for skull size (NBV) was measured using automated segmentation (SIENAX). Change in CCV and NBV was measured by subtraction of baseline from serial CCV and SIENAX images; in addition, percentage brain volume change relative to baseline was measured directly using a registration-based method (SIENA). Sample sizes for given treatment effects and power were calculated for standard analyses using parameters estimated from the sample. RESULTS: For a 2-year trial duration, minimum sample sizes per arm required to detect a 50% treatment effect at 80% power were 32 for SIENA, 69 for CCV, and 273 for SIENAX. Two-year minimum sample sizes were smaller than 1-year by 71% for SIENAX, 55% for CCV, and 44% for SIENA. CONCLUSION: SIENA and central cerebral volume are feasible outcome measures for inclusion in placebo-controlled trials in secondary progressive multiple sclerosis.