Lehman, V. T., Brinjikji, W., Mossa-Basha, M., Lanzino, G., Rabinstein, A. A., Kallmes, D. F., & Huston, J. (2018). Conventional and high-resolution vessel wall MRI of intracranial aneurysms: current concepts and new horizons. Journal of Neurosurgery, 128(4), 969–981. https://doi.org/10.3171/2016.12.JNS162262

3D techniques are state-of-the-art, with advantages that include higher through-plane spatial resolution, with increased brain coverage, and the ability to perform isotropic acquisitions. Variable refocusing flip angle (VRFA) techniques are the most extensively studied and now predominate many clinical practices (sampling perfection with application optimized contrast using different flip angle evolutions [SPACE], Siemens Healthcare; CUBE, GE; and volumetric isotropic turbo spin echo acquisition [VISTA], Philips Healthcare) as they provide improved blood suppression in a shortened scan time relative to other 3D and 2D techniques.

There are a variety of blood and CSF suppression techniques which can be used to enhance visualization of the vessel wall. CSF suppression techniques include antidrive and delayed alternating with nutation for tailored excitation (DANTE), while blood suppression techniques include motion sensitive driven equilibrium (MSDE), DANTE, double inversion recovery (DIR), quadruple inversion recovery (QIR), and magnetization-prepared inversion recovery (MPIR). While some suppression techniques are used with 3D high-resolution vessel wall imaging (HR-VWI) (MSDE, DANTE, antidrive), others can only be used with 2D techniques (DIR, QIR).

The HR-VWI demonstrated in this article is a 3D PD SPACE technique, acquired with a 16-cm FOV. This technique allows 0.25 mm × 0.25 mm interpolated in-plane pixel size with a slice thickness of 0.5 mm and can be acquired in any imaging plane. This focused technique only covers a 6-cm slab of brain, so care is required to cover the region of interest.

The current literature suggests that saccular aneurysms with wall enhancement on HR-VWI are frequently unstable (changing morphology, symptomatic, or ruptured) and that more urgent treatment may be reasonable whereas the preponderance of saccular aneurysms without wall enhancement appears to be stable and that less urgent treatment or observation may be reasonable. However, these assertions are based on retrospective data that include relatively large percentages of ruptured aneurysms, which selects for aneurysms with wall enhancement, with relatively fewer data on unstable unruptured aneurysms. The pathological basis for vessel wall enhancement has been presumed to represent inflammation and/or proliferation of vasa vasorum. The finding of strong focal enhancement of the aneurysm apex which is associated with the point of rupture raises the possibility that enhancement could help identify the ruptured aneurysm when multiple aneurysms are present. A case series including 3 patients with multiple aneurysms provides initial evidence that HR-VWI can identify the culprit aneurysm in the setting of acute SAH. This observation is important because the distribution of SAH is not highly predictive of aneurysm location. This information could also triage acute treatment toward the culprit aneurysm. In chronic fusiform vertebrobasilar aneurysms, T1 hyperintensity consistent with recent hemorrhage is associated with an increased likelihood of growth. Many other aneurysm features associated with growth have been identified, including intramural thrombus, the presence of daughter sacs, and overall size.

Initial studies of HR-VWI of intracranial dissection have shown that features of dissection including an intimal flap, double lumen, and intramural hematoma can be identified, including cases with dissecting aneurysms. Both the wall of the lumen and outer margin of the artery can enhance; a small portion of intramural hematomas also reportedly enhance.

Much more to this review, also discussing myxomatous and mycotic aneurysms, blood-blister aneurysms.

8 Figures

Velly, L., Perlbarg, V., Boulier, T., Adam, N., Delphine, S., Luyt, C. E., … Patassini, M. (2018). Use of brain diffusion tensor imaging for the prediction of long-term neurological outcomes in patients after cardiac arrest: a multicentre, international, prospective, observational, cohort study. The Lancet Neurology, 17(4), 317–326. https://doi.org/10.1016/S1474-4422(18)30027-9

The aim of this study was to assess whether quantitative whole-brain white matter fractional anisotropy (WWM-FA) measured by diffusion tensor imaging between day 7 and day 28 after cardiac arrest can predict long-term neurological outcome.

This prospective, observational, cohort study (part of the MRI-COMA study) was done in 14 centers in France, Italy, and Belgium. They enrolled patients aged 18 years or older who had been unconscious for at least 7 days after cardiac arrest into the derivation cohort. The following year, they recruited the validation cohort on the same basis. They also recruited a minimum of five healthy volunteers at each center for the normalization procedure. Whole-brain white matter fractional anisotropy values were compared with standard criteria for unfavorable outcome, conventional MRI sequences (FLAIR and DWI), and proton MR spectroscopy. The primary outcome was the best achieved Glasgow-Pittsburgh Cerebral Performance Categories (CPC) at 6 months, dichotomized as favorable (CPC 1–2) and unfavorable outcome (CPC 3–5).

Between Oct 2006, and June 2014, 185 patients were enrolled in the derivation cohort, of whom 150 had an interpretable multimodal MRI and were included in the analysis. 33 (22%) patients had a favorable neurological outcome at 6 months. Prognostic accuracy, as quantified by the area under the ROC curve, was significantly higher with the normalized whole-brain white matter fractional anisotropy value than with the standard criteria for unfavorable outcome or other MRI sequences. In a subsequent validation cohort of 50 patients (enrolled between April 2015, and March 2016), a normalized whole-brain white matter fractional anisotropy value lower than 0.91, set from the derivation cohort, had a negative predictive value of 71.4% and a positive predictive value of 100%, with 89.7% sensitivity and 100% specificity for the prediction of unfavorable outcome. They conclude that in patients who are unconscious 7 days after cardiac arrest, the normalized whole-brain white matter fractional anisotropy value, measured by diffusion tensor imaging, could be used to accurately predict neurological outcome at 6 months.

MRI acquisitions were done between day 7 and day 28 after cardiac arrest on 15 scanners from three manufacturers: GE Medical Systems (Milwaukee, WI, USA), Siemens Medical Solutions (Erlangen, Germany), and Philips Medical Systems (Eindhoven, Netherlands). DTI, ¹H-MRS, and several conventional MRI sequences, including FLAIR and DWI, were acquired. Healthy volunteers and patients underwent the same imaging protocol. Importantly, the raw value of each derived diffusion measure was divided by the mean of this measure across healthy controls, acquired in the same scanner with the same sequence. Results are thus expressed as a percentage of controls.

2 Figures, 3 Tables (no images)

Beecher, J. S., Lyon, K., Ban, V. S., Vance, A., McDougall, C. M., Whitworth, L. A., … Welch, B. G. (2017). Delayed treatment of ruptured brain AVMs: is it ok to wait? Journal of Neurosurgery, 128(April), 1–7. https://doi.org/10.3171/2017.1.JNS16745

The natural history of a ruptured AVM entails a 6%– 15.8% risk of rehemorrhage in the 1st year. This range is what neurosurgeons refer to when determining the management of a patient with a ruptured AVM. Although the rerupture risk diminishes after the 1st year to 1.7%–6.2% per year, cumulatively this risk of rehemorrhage often indicates intervention is warranted to prevent further neurological sequalae. The present guidelines for AVM treatment suggest that treatment take place in an elective manner but does not specify a protocol. This study sought to determine the safety of treating a ruptured AVM beyond the subacute period that was defined as 4 weeks.

Patients presenting to the authors’ institution from January 2000 to December 2015 with ruptured brain AVMs treated at least 4 weeks posthemorrhage were included in this analysis. Exclusion criteria were ruptured AVMs that required emergency surgery involving resection of the AVM, prior treatment of AVM at another institution, or treatment of lesions within 4 weeks for other reasons (subacute surgery). The primary outcome measure was time from initial hemorrhage to treatment failure (defined as rehemorrhage or neurological decline as a direct result of the AVM).

Of 102 ruptured AVMs in 102 patients meeting inclusion criteria, 6.9% failed the treatment paradigm. Six patients (5.8%) had a new hemorrhage within a median of 248 days. The total “at risk” period was 18,740 patient-days, yielding a rehemorrhage rate of 11.5% per patient-year, or 0.96% per patient-month. Twelve (11.8%) of 102 patients were found to have an associated aneurysm. In this group there was a single (8.3%) new hemorrhage during a total at-risk period of 263 patient-days until the aneurysm was secured, yielding a rehemorrhage risk of 11.4% per patient-month.

These findings indicate that delaying intervention for at least 4 weeks after the initial hemorrhage subjects the patient to a low (< 1%) risk of rehemorrhage. The authors modified the treatment paradigm when a high-risk feature, such as an associated intracranial aneurysm, was identified.

Salahuddin, H., Ramaiah, G., Slawski, D. E., Shawver, J., Buehler, M., Zaidi, S. F., & Jumaa, M. (2018). Mechanical thrombectomy of M1 and M2 middle cerebral artery occlusions. Journal of NeuroInterventional Surgery, 10(4), 330–334. https://doi.org/10.1136/neurintsurg-2017-013159

The objective of the study was to determine if MT of M2 occlusion is as safe and efficacious as current standard-of-care MT for M1 occlusions. The authors retrospectively reviewed records of 212 patients undergoing MT for isolated MCA M1 or M2 occlusions during a 36-month period (Sept 2013 to Sept 2016) at two centers. Treatment variables, clinical outcomes, and complications in each group were recorded. There were 153 M1 MCA occlusions and 59 M2 MCA occlusions. No statistically significant difference was found in the rate of mortality (20% in M1 vs 13.6% in M2), excellent (34.5% vs 37.3%) or good (51% vs 55.9%) clinical outcomes between the two groups. Infarct volumes (48.4 mL vs 46.2 mL) were comparable between the two groups, as were the rates of hemorrhagic (3.3% vs 3.4%) and procedural complications (3.3% vs 5.1%).

In conclusion, this study demonstrates that clinical outcomes, radiographic outcomes, and rates of procedural and hemorrhagic complications are comparable between patients with M1 and M2 occlusions who were selected by similar criteria and treated with the same endovascular techniques with second-generation MT devices. Similar clinical outcomes have been shown in multiple other studies and a post hoc analysis of the STAR, SWIFT, and SWIFT PRIME studies.

Mangeat, G., Badji, A., Ouellette, R., Treaba, C. A., Herranz, E., Granberg, T., … Cohen-Adad, J. (2018). Changes in structural network are associated with cortical demyelination in early multiple sclerosis. Human Brain Mapping, 39(5), 2133–2146. https://doi.org/10.1002/hbm.23993

The aim of this study was to investigate the interplay between structural connectivity and cortical demyelination in early multiple sclerosis. 27 multiple sclerosis patients and 18 age-matched controls underwent two MRI scanning sessions. The first was done at 7T and involved acquiring quantitative T1 and T2* high-resolution maps to estimate cortical myelination. The second was done on a Connectom scanner and consisted of acquiring high angular resolution diffusion-weighted images to compute white matter structural connectivity metrics: strength, clustering and local efficiency. To further investigate the interplay between structural connectivity and cortical demyelination, patients were divided into four groups according to disease-duration: 0–1 year, 1–2 years, 2–3 years, and >3 years. ANOVA and Spearman’s correlations were used to highlight relations between metrics. ANOVA detected a significant effect between disease duration and both cortical myelin and connectivity metrics. They observed significant cortical myelin loss in the shorter disease-duration cohorts (0–1 year), and an increase in connectivity in the longer disease-duration cohort (2–3 years). Additonally, significant covariations between myelin estimation and white matter connectivity metrics were observed.

They conclude that an association between cortical myelin loss and changes in white matter connectivity in early multiple sclerosis was detected. These changes in network organization might be the result of compensatory mechanisms in response to the ongoing cortical diffuse damage in the early stages of multiple sclerosis.

7 Figures, 1 table

Geraldes, R., Ciccarelli, O., Barkhof, F., De Stefano, N., Enzinger, C., Filippi, M., … Palace, J. (2018). The current role of MRI in differentiating multiple sclerosis from its imaging mimics. Nature Reviews Neurology, 14(4), 199–213. https://doi.org/10.1038/nrneurol.2018.14

A MAGNIMS workshop (European Magnetic Resonance Network in MS) was held for three purposes. The first purpose was to update the imaging features that differentiate between MS and its most common imaging mimics, particularly age-related cerebrovascular disease and NMOSD (including anti-MOG antibody-associated disease), on 1.5–3T conventional MRI using clinical diagnostic sequences (for example, T2‑weighted MRI and T2‑weighted FLAIR), and pre-contrast and post-contrast T1-weighted images.

The second purpose of the workshop was to determine the utility of other MRI techniques, such as susceptibility-weighted imaging (SWI) double inversion recovery (DIR), proton magnetic resonance spectroscopy (MRS), magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI), which appear promising for identifying disease-specific features. Finally, they also examined advances that have been made in identifying imaging hallmarks that can differentiate relatively uncommon MS mimics from MS. In this Review, they present the findings of this workshop in relation to the use of MRI to distinguish MS from other white matter disorders and propose a practical diagnostic algorithm.

As you know, specific MRI features can help to make alternative diagnoses when MS is suspected. Macrobleeds or microbleeds, infarcts, WMLs that spare the U‑fibers and siderosis suggest cerebrovascular disease. Extensive spinal cord lesions are useful in distinguishing NMOSD from MS, and the presence of meningeal enhancement, increasing lesion size over time, calcifications, complete ring enhancement and strictly symmetrical WMLs suggest a diagnosis other than MS. These features should be systematically excluded, and we suggest the simple mnemonic ‘iMIMICS’ to represent the imaging red flags. The mnemonic stands for: patterns of meningeal (M) enhancement; indistinct (I) border or increasing (I) lesion size; the presence of macrobleeds (M) or microbleeds (M); the presence of cortical or lacunar infarcts (I); the presence of cavities (C), complete (C) ring enhancement or calcifications (C); and symmetrical (S) lesions, lesions that spare (S) the U‑fibers, siderosis, and spinal (S) cord extensive lesions.

4 Tables, 5 Figures

Goyal, N., Tsivgoulis, G., Frei, D., Turk, A., Baxter, B., Froehler, M. T., … Arthur, A. S. (2018). Comparative safety and efficacy of combined IVT and MT with direct MT in large vessel occlusion. Neurology, 90(15), e1274–e1282. https://doi.org/10.1212/WNL.0000000000005299

In this multicenter study, the authors sought to evaluate comparative safety and efficacy of combined IV thrombolysis (IVT) and mechanical thrombectomy (MT) vs direct MT in emergent large vessel occlusion (ELVO) patients.

Consecutive ELVO patients treated with MT at 6 high-volume endovascular centers were evaluated. Standard safety and efficacy outcomes (successful reperfusion [modified Thrombolysis in Cerebral Infarction IIb/III], functional independence [FI] [modified Rankin Scale (mRS) score of 0–2 at 3 months], favorable functional outcome [mRS of 0–1 at 3 months], functional improvement [mRS shift by 1-point decrease in mRS score]) were compared between patients who underwent combined IVT and MT vs MT alone. A total of 292 and 277 patients were treated with combination therapy and direct MT, respectively. The combination therapy group had greater functional improvement at 3 months. After propensity score matching, 104 patients in the direct MT group were matched to 208 patients in the combination therapy group. IVT pretreatment was independently associated with higher odds of FI and functional improvement. This study provides Class III evidence that for stroke patients with emergent large vessel occlusion, combined IVT and MT is superior to direct MT in improving functional outcomes.

The authors conclude that this multicenter study indicates that pretreatment with IVT prior to MT in eligible ELVO patients is associated with greater functional improvement, higher odds of FI, and lower odds of mortality at 3 months compared to direct MT subgroups of patients who were matched for baseline characteristics. The former associations were independent of demographics, baseline stroke severity, location of occlusion, and symptom onset to groin puncture time.

5 Tables

Villemagne, V. L., Doré, V., Burnham, S. C., Masters, C. L., & Rowe, C. C. (2018). Imaging tau and amyloid-β proteinopathies in Alzheimer disease and other conditions. Nature Reviews Neurology, 14(4), 225–236. https://doi.org/10.1038/nrneurol.2018.9

March 2018 podcast showcased a different review of PET agents (Payoux P, Salabert AS. New PET markers for the diagnosis of dementia. Curr Opin Neurol. 2017;30(6):1) so I won’t go into those again.  But this review in Nat Rev Neurology is excellent.

A couple of interesting points from this review:

Key challenges from a clinical point of view in the diagnosis of neurodegenerative conditions are that a single disease phenotype can be caused by different aggregated proteins and that a single aggregated protein can be the underlying cause of several clinically different diseases. For example, post-mortem studies of patients with a clinical diagnosis of Alzheimer disease (AD) do not always find both of the two pathological hallmarks of the disease — namely, tau intracellular neurofibrillary tangles (NFTs) and extracellular amyloid‑β (Αβ) plaques — casting doubt on the accuracy of the clinical diagnosis. Moreover, several aggregated protein species are often present in the same individual, and other aggregated proteins can coexist with tau and Aβ. For example, patients with both Lewy bodies (α‑synuclein aggregates in neurons) and Aβ plaques might have a clinical diagnosis of AD, dementia with Lewy bodies (DLB), Parkinson disease (PD) or PD dementia (PDD). In this context, the introduction of in vivo brain imaging of patients with neurodegenerative disorders, in particular the advent of Aβ imaging, has revolutionized the diagnosis and management of these diseases. These beneficial effects are likely to be extended further by the introduction of selective tau imaging.

In PET studies, ~25–35% of elderly individuals with normal performance on cognitive tests have high levels of cortical 11C-PiB retention, predominantly in the posterior cingulate, precuneus and prefrontal regions. These findings are in perfect agreement with post-mortem reports showing that ~25% of non-demented individuals aged ≥75 years have Aβ plaques, probably representing preclinical AD. Furthermore, the prevalence of high 11C-PiB retention has increased each decade at the same rate as the increase in prevalence of plaques in non-demented individuals in post-mortem studies. The detection of Aβ pathology in asymptomatic individuals before the development of AD is of crucial importance because it is precisely this group who could benefit the most from therapies aimed at reducing or eliminating Αβ from the brain before irreversible synaptic or neuronal loss occurs.

People with MCI comprise a heterogeneous group with a wide spectrum of underlying pathologies. In ~40–60% of patients with carefully characterized MCI, the criteria for AD are usually met within the subsequent 3–4 years. Αβ imaging is useful for discriminating between individuals with MCI who do and do not have AD pathology. Approximately 50–70% of individuals with MCI have high levels of cortical 11C-PiB retention, and this group is now classed as having either MCI due to AD or prodromal AD. The lack of a strong correlation between Aβ deposition and measures of cognition, synaptic activity and neurodegeneration in patients with AD, in addition to the evidence of Αβ deposition in a high percentage of patients with MCI and asymptomatic healthy controls, collectively suggest that Αβ deposition is an early and necessary (although by itself, not sufficient) cause of cognitive decline in AD.