Are Dynamic Arterial Spin-Labeling MRA and Time-Resolved Contrast-Enhanced MRA Suited for Confirmation of Obliteration following Gamma Knife Radiosurgery of Brain Arteriovenous Malformations?

BACKGROUND AND PURPOSE: Intra-arterial DSA has been traditionally used for confirmation of cure following gamma knife radiosurgery for AVMs. Our aim was to evaluate whether 4D arterial spin-labeling MRA and contrast-enhanced time-resolved MRA in combination can be an alternative to DSA for confirmation of AVM obliteration following gamma knife radiosurgery. MATERIALS AND METHODS: In this prospective study, 30 patients undergoing DSA for confirmation of obliteration following gamma knife radiosurgery for AVMs (criterion standard) also underwent MRA, including arterial spin-labeling MRA and contrast-enhanced time-resolved MRA. One dataset was technically unsatisfactory, and the case was excluded. The DSA and MRA datasets of 29 patients were independently and blindly evaluated by 2 observers regarding the presence/absence of residual AVMs. RESULTS: The mean time between gamma knife radiosurgery and follow-up DSA/MRA was 53 months (95% CI, 42-64 months; range, 22-168 months). MRA total scanning time was 9 minutes and 17 seconds. Residual AVMs were detected on DSA in 9 subjects (obliteration rate = 69%). All residual AVMs were detected on at least 1 MRA sequence. Arterial spin-labeling MRA and contrast-enhanced time-resolved MRA showed excellent specificity and positive predictive values individually (100%). However, their sensitivity and negative predictive values were suboptimal due to 1 false-negative with arterial spin-labeling MRA and 2 with contrast-enhanced time-resolved MRA (sensitivity = 88% and 77%, negative predictive values = 95% and 90%, respectively). Both sensitivity and negative predictive values increased to 100% if a composite assessment of both MRA sequences was performed. Diagnostic accuracy (receiver operating characteristic) and agreement (κ) are maximized using arterial spin-labeling MRA and contrast-enhanced time-resolved MRA in combination (area under receiver operating characteristic curve = 1, P < .001; κ = 1, P < .001, respectively). CONCLUSIONS: Combining arterial spin-labeling MRA with contrast-enhanced time-resolved MRA holds promise as an alternative to DSA for confirmation of obliteration following gamma knife radiosurgery for brain AVMs, having provided 100% sensitivity and specificity in the study. Their combined use also enables reliable characterization of residual lesions.

Italian consensus recommendations for a biomarker-based aetiological diagnosis in mild cognitive impairment patients.

BACKGROUND AND PURPOSE: Biomarkers support the aetiological diagnosis of neurocognitive disorders in vivo. Incomplete evidence is available to drive clinical decisions; available diagnostic algorithms are generic and not very helpful in clinical practice. The aim was to develop a biomarker-based diagnostic algorithm for mild cognitive impairment patients, leveraging on knowledge from recognized national experts. METHODS: With a Delphi procedure, experienced clinicians making variable use of biomarkers in clinical practice and representing five Italian scientific societies (neurology - Società Italiana di Neurologia per le Demenze; neuroradiology - Associazione Italiana di Neuroradiologia; biochemistry - Società Italiana di Biochimica Clinica; psychogeriatrics - Associazione Italiana di Psicogeriatria; nuclear medicine - Associazione Italiana di Medicina Nucleare) defined the theoretical framework, relevant literature, the diagnostic issues to be addressed and the diagnostic algorithm. An N-1 majority defined consensus achievement. RESULTS: The panellists chose the 2011 National Institute on Aging and Alzheimer's Association diagnostic criteria as the reference theoretical framework and defined the algorithm in seven Delphi rounds. The algorithm includes baseline clinical and cognitive assessment, blood examination, and magnetic resonance imaging with exclusionary and inclusionary roles; dopamine transporter single-photon emission computed tomography (if no/unclear parkinsonism) or metaiodobenzylguanidine cardiac scintigraphy for suspected dementia with Lewy bodies with clear parkinsonism (round VII, votes (yes-no-abstained): 3-1-1); 18 F-fluorodeoxyglucose positron emission tomography for suspected frontotemporal lobar degeneration and low diagnostic confidence of Alzheimer's disease (round VII, 4-0-1); cerebrospinal fluid for suspected Alzheimer's disease (round IV, 4-1-0); and amyloid positron emission tomography if cerebrospinal fluid was not possible/accepted (round V, 4-1-0) or inconclusive (round VI, 5-0-0). CONCLUSIONS: These consensus recommendations can guide clinicians in the biomarker-based aetiological diagnosis of mild cognitive impairment, whilst guidelines cannot be defined with evidence-to-decision procedures due to incomplete evidence.

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.

A visual quality control scale for clinical arterial spin labeling images.

BACKGROUND: Image-quality assessment is a fundamental step before clinical evaluation of magnetic resonance images. The aim of this study was to introduce a visual scoring system that provides a quality control standard for arterial spin labeling (ASL) and that can be applied to cerebral blood flow (CBF) maps, as well as to ancillary ASL images. METHODS: The proposed image quality control (QC) system had two components: (1) contrast-based QC (cQC), describing the visual contrast between anatomical structures; and (2) artifact-based QC (aQC), evaluating image quality of the CBF map for the presence of common types of artifacts. Three raters evaluated cQC and aQC for 158 quantitative signal targeting with alternating radiofrequency labelling of arterial regions (QUASAR) ASL scans (CBF, T1 relaxation rate, arterial blood volume, and arterial transient time). Spearman correlation coefficient (r), intraclass correlation coefficients (ICC), and receiver operating characteristic analysis were used. RESULTS: Intra/inter-rater agreement ranged from moderate to excellent; inter-rater ICC was 0.72 for cQC, 0.60 for aQC, and 0.74 for the combined QC (cQC + aQC). Intra-rater ICC was 0.90 for cQC; 0.80 for aQC, and 0.90 for the combined QC. Strong correlations were found between aQC and CBF maps quality (r = 0.75), and between aQC and cQC (r = 0.70). A QC score of 18 was optimal to discriminate between high and low quality clinical scans. CONCLUSIONS: The proposed QC system provided high reproducibility and a reliable threshold for discarding low quality scans. Future research should compare this visual QC system with an automatic QC system.

Heterogeneity of Cortical Lesion Susceptibility Mapping in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping has been used to characterize iron and myelin content in the deep gray matter of patients with multiple sclerosis. Our aim was to characterize the susceptibility mapping of cortical lesions in patients with MS and compare it with neuropathologic observations. MATERIALS AND METHODS: The pattern of microglial activation was studied in postmortem brain tissues from 16 patients with secondary-progressive MS and 5 age-matched controls. Thirty-six patients with MS underwent 3T MR imaging, including 3D double inversion recovery and 3D-echo-planar SWI. RESULTS: Neuropathologic analysis revealed the presence of an intense band of microglia activation close to the pial membrane in subpial cortical lesions or to the WM border of leukocortical cortical lesions. The quantitative susceptibility mapping analysis revealed 131 cortical lesions classified as hyperintense; 33, as isointense; and 84, as hypointense. Quantitative susceptibility mapping hyperintensity edge found in the proximity of the pial surface or at the white matter/gray matter interface in some of the quantitative susceptibility mapping-hyperintense cortical lesions accurately mirrors the microglia activation observed in the neuropathology analysis. CONCLUSIONS: Cortical lesion susceptibility maps are highly heterogeneous, even at individual levels. Quantitative susceptibility mapping hyperintensity edge found in proximity to the pial surface might be due to the subpial gradient of microglial activation.

Epilepsy in multiple sclerosis: The role of temporal lobe damage.

BACKGROUND: Although temporal lobe pathology may explain some of the symptoms of multiple sclerosis (MS), its role in the pathogenesis of seizures has not been clarified yet. OBJECTIVES: To investigate the role of temporal lobe damage in MS patients suffering from epilepsy, by the application of advanced multimodal 3T magnetic resonance imaging (MRI) analysis. METHODS: A total of 23 relapsing remitting MS patients who had epileptic seizures (RRMS/E) and 23 disease duration matched RRMS patients without any history of seizures were enrolled. Each patient underwent advanced 3T MRI protocol specifically conceived to evaluate grey matter (GM) damage. This includes grey matter lesions (GMLs) identification, evaluation of regional cortical thickness and indices derived from the Neurite Orientation Dispersion and Density Imaging model. RESULTS: Regional analysis revealed that in RRMS/E, the regions most affected by GMLs were the hippocampus (14.2%), the lateral temporal lobe (13.5%), the cingulate (10.0%) and the insula (8.4%). Cortical thinning and alteration of diffusion metrics were observed in several regions of temporal lobe, in insular cortex and in cingulate gyrus of RRMS/E compared to RRMS ( p< 0.05 for all comparisons). CONCLUSIONS: Compared to RRMS, RRMS/E showed more severe damage of temporal lobe, which exceeds what would be expected on the basis of the global GM damage observed.

Does the intravenous administration of frusemide reduce endolymphatic hydrops?

OBJECTIVE: To verify the hypothesis that intravenous frusemide reduces endolymphatic hydrops, as evaluated by three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging following intratympanic gadolinium administration. METHODS: The study comprised 12 patients (7 females and 5 males, aged 19-74 years) with Ménière's disease. Disease duration ranged from 0.5 to 8 years, with a frequency of 0.5 to 6 vertigo spells per month, as calculated in the last 6 months. Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging was performed 24 hours after intratympanic injection of gadobutrol diluted eight-fold. Frusemide 20 mg was given intravenously immediately after imaging. Magnetic resonance imaging was repeated after 1 hour, using the same parameters and sequence. RESULTS: All patients showed enhancement defects, indicating endolymphatic hydrops of variable degrees. No modifications occurred at the second magnetic resonance imaging performed 1 hour after frusemide administration. CONCLUSION: There was no evidence of endolymphatic hydrops modification 1 hour after intravenously administered frusemide. Therefore, loop diuretics in Ménière's disease, which are today used on an empirical basis, must be reconsidered. Implications of these outcomes are discussed and related to the role of endolymphatic hydrops in the development of Ménière's disease.

A neuroradiologist's guide to arterial spin labeling MRI in clinical practice.

Arterial spin labeling (ASL) is a non-invasive MRI technique to measure cerebral blood flow (CBF). This review provides a practical guide and overview of the clinical applications of ASL of the brain, as well its potential pitfalls. The technical and physiological background is also addressed. At present, main areas of interest are cerebrovascular disease, dementia and neuro-oncology. In cerebrovascular disease, ASL is of particular interest owing to its quantitative nature and its capability to determine cerebral arterial territories. In acute stroke, the source of the collateral blood supply in the penumbra may be visualised. In chronic cerebrovascular disease, the extent and severity of compromised cerebral perfusion can be visualised, which may be used to guide therapeutic or preventative intervention. ASL has potential for the detection and follow-up of arteriovenous malformations. In the workup of dementia patients, ASL is proposed as a diagnostic alternative to PET. It can easily be added to the routinely performed structural MRI examination. In patients with established Alzheimer's disease and frontotemporal dementia, hypoperfusion patterns are seen that are similar to hypometabolism patterns seen with PET. Studies on ASL in brain tumour imaging indicate a high correlation between areas of increased CBF as measured with ASL and increased cerebral blood volume as measured with dynamic susceptibility contrast-enhanced perfusion imaging. Major advantages of ASL for brain tumour imaging are the fact that CBF measurements are not influenced by breakdown of the blood-brain barrier, as well as its quantitative nature, facilitating multicentre and longitudinal studies.

Effect of median-nerve electrical stimulation on BOLD activity in acute ischemic stroke patients.

OBJECTIVE: To investigate blood oxygenation level-dependent (BOLD) activation during somatosensory electrical stimulation of the median nerve in acute stroke patients and to determine its correlation with ischemic damage and clinical recovery over time. METHODS: Fourteen acute stroke patients underwent functional magnetic resonance imaging (fMRI) during contralesional median-nerve electrical stimulation 12-48 h after stroke. Findings were then validated by diffusion tensor imaging (DTI) and motor evoked potential by transcranial magnetic stimulation (TMS). RESULTS: Poor clinical recovery at three months was noted in four patients with no activation in the early days after stroke, whereas good clinical recovery was observed in eight patients with a normal activation pattern in the primary sensory motor area in the acute phase. In two patients BOLD activation correlated weakly with clinical recovery. Findings from TMS and DTI partially correlated with clinical recovery and functional scores. CONCLUSIONS: Clinically relevant insights into the "functional reserve" of stroke patients gained with peripheral nerve stimulation during fMRI may carry prognostic value already in the acute period of a cerebrovascular accident. SIGNIFICANCE: BOLD activation maps could provide insights into the functional organization of the residual systems and could contribute to medical decision making in neurological and rehabilitative treatment.

Updates in the determination of brain death.

The concept of brain death must be accurately determined and defined, especially in the light of the latest legislation on brain blood flow measurements.

Diffusion tensor tracking of callosal fibers several years after callosotomy.

Diffusion tensor imaging (DTI) can provide more detailed in vivo information on the structural preservation of transected white matter tracts than conventional imaging methods. Here we show for the first time tracks of severed callosal fibers up to 17 years from resection. Five patients subjected to complete or partial callosotomy several years before the study were examined with DTI and compared to a normal control. Transected fibers were traced in all patients and were more clearly visible in the anterior and posterior parts than in the middle of the commissure. These findings suggest that microstructural changes persist for many years in the severed fibers, as also reflected by fractional anisotropy and apparent diffusion coefficient values, enabling a reconstruction of the longitudinal organization of severed central tracts that could not be achieved with previous techniques.

Review of corpus callosum topography, analysis of diffusion values for the different callosal fibers and sex differences.

Conventional MRI shows the morphology of the corpus callosum (CC), but does not reveal cortical connectivity or structural information on the CC. Here, we applied diffusion tensor imaging (DTI) in conjunction with a tract-tracing algorithm to incorporate cortical connectivity information on the CC in 40 subjects and to detect the main area and sex structural differences. CC parcellation was based on trajectories to different cortical (prefrontal, frontal motor/premotor/supplementary motor connections, parieto-occipital, temporal) and sub-cortical areas (capsular/basal ganglia connections). In agreement with recent DTI studies, we found that motor fibers occupy a much larger portion of the CC than previously believed on the basis of anatomical data. Differences in anisotropy values were instead in agreement with previous morphological evidence of smaller fibers in the anterior and posterior portions of the CC. The main sex difference was observed in anisotropy values in frontal fibers that proved to be lower in females than in males. Statistically significant differences in the regional diffusion parameters and between sexes give rise to many important questions regarding fiber organization patterns, CC microstructure and the functional relevance of these differences and provide evidence for the role of DTI, which reaches beyond the information given by morphological analysis.