Background Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid beta in the cerebrovascular wall. The Boston... Show moreBackground Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid beta in the cerebrovascular wall. The Boston criteria are used worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report an international collaborative study aiming to update and externally validate the Boston diagnostic criteria across the full spectrum of clinical CAA presentations.Methods In this multicentre, hospital-based, retrospective, MRI and neuropathology diagnostic accuracy study, we did a retrospective analysis of clinical, radiological, and histopathological data available to sites participating in the International CAA Association to formulate updated Boston criteria and establish their diagnostic accuracy across different populations and clinical presentations. Ten North American and European academic medical centres identified patients aged 50 years and older with potential CAA-related clinical presentations (ie, spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathological assessment for CAA diagnosis. MRI scans were centrally rated at Massachusetts General Hospital (Boston, MA, USA) for haemorrhagic and non-haemorrhagic CAA markers, and brain tissue samples were rated by neuropathologists at the contributing sites. We derived the Boston criteria version 2.0 (v2.0) by selecting MRI features to optimise diagnostic specificity and sensitivity in a prespecified derivation cohort (Boston cases 1994-2012, n=159), then externally validated the criteria in a prespecified temporal validation cohort (Boston cases 2012-18, n=59) and a geographical validation cohort (non-Boston cases 2004-18; n=123), comparing accuracy of the new criteria to the currently used modified Boston criteria with histopathological assessment of CAA as the diagnostic standard. We also assessed performance of the v2.0 criteria in patients across all cohorts who had the diagnostic gold standard of brain autopsy.Findings The study protocol was finalised on Jan 15, 2017, patient identification was completed on Dec 31, 2018, and imaging analyses were completed on Sept 30, 2019. Of 401 potentially eligible patients presenting to Massachusetts General Hospital, 218 were eligible to be included in the analysis; of 160 patient datasets from other centres, 123 were included. Using the derivation cohort, we derived provisional criteria for probable CAA requiring the presence of at least two strictly lobar haemorrhagic lesions (ie, intracerebral haemorrhages, cerebral microbleeds, or foci of cortical superficial siderosis) or at least one strictly lobar haemorrhagic lesion and at least one white matter characteristic (ie, severe visible perivascular spaces in centrum semiovale or white matter hyperintensities in a multispot pattern). The sensitivity and specificity of these criteria were 74.8% (95% CI 65.4-82.7) and 84.6% (71.9-93.1) in the derivation cohort, 92.5% (79.6-98.4) and 89.5% (66.9-98.7) in the temporal validation cohort, 80.2% (70.8-87.6) and 81.5% (61.9-93.7) in the geographical validation cohort, and 74.5% (65.4-82.4) and 95.0% (83.1-99.4) in all patients who had autopsy as the diagnostic standard. The area under the receiver operating characteristic curve (AUC) was 0.797 (0.732-0.861) in the derivation cohort, 0.910 (0.828-0.992) in the temporal validation cohort, 0.808 (0.724-0.893) in the geographical validation cohort, and 0.848 (0.794-0.901) in patients who had autopsy as the diagnostic standard. The v2.0 Boston criteria for probable CAA had superior accuracy to the current Boston criteria (sensitivity 64.5% [54.9-73.4]; specificity 95.0% [83.1-99.4]; AUC 0.798 [0.741-0854]; p=0.0005 for comparison of AUC) across all individuals who had autopsy as the diagnostic standard.Interpretation The Boston criteria v2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their specificity in our cohorts of patients aged 50 years and older presenting with spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes. Future studies will be needed to determine generalisability of the v.2.0 criteria across the full range of patients and clinical presentations. Show less
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... Show moreCombining 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.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 (?) are maximized using arterial spin-labeling MRA and contrast-enhanced time-resolved MRA in combination (area under receiver operating characteristic curve?= 1, P??=?1, P? Show less
Rojas-Villabona, A.; Sokolska, M.; Solbach, T.; Grieve, J.; Rega, M.; Torrealdea, F.; ... ; Jager, H.R. 2021
PurposeIntra-arterial Digital Subtraction Angiography (DSA) is the gold standard technique for radiosurgery target delineation in brain Arterio-Venous Malformations (AVMs). This study aims to... Show morePurposeIntra-arterial Digital Subtraction Angiography (DSA) is the gold standard technique for radiosurgery target delineation in brain Arterio-Venous Malformations (AVMs). This study aims to evaluate whether a combination of three Magnetic Resonance Angiography sequences (triple-MRA) could be used for delineation of brain AVMs for Gamma Knife Radiosurgery (GKR).MethodsFifteen patients undergoing DSA for GKR targeting of brain AVMs also underwent triple-MRA: 4D Arterial Spin Labelling based angiography (ASL-MRA), Contrast-Enhanced Time-Resolved MRA (CE-MRA) and High Definition post-contrast Time-Of-Flight angiography (HD-TOF). The arterial phase of the AVM nidus was delineated on triple-MRA by an interventional neuroradiologist and a consultant neurosurgeon (triple-MRA volume). Triple-MRA volumes were compared to AVM targets delineated by the clinical team for delivery of GKR using the current planning paradigm, i.e., stereotactic DSA and volumetric MRI (DSA volume). Difference in size, degree of inclusion (DI) and concordance index (CcI) between DSA and triple-MRA volumes are reported.ResultsAVM target volumes delineated on triple-MRA were on average 9.8% smaller than DSA volumes (95%CI:5.6-13.9%; SD:7.14%; p = .003). DI of DSA volume in triple-MRA volume was on average 73.5% (95%CI:71.2-76; range: 65-80%). The mean percentage of triple-MRA volume not included on DSA volume was 18% (95%CI:14.7-21.3; range: 7-30%).ConclusionThe technical feasibility of using triple-MRA for visualisation and delineation of brain AVMs for GKR planning has been demonstrated. Tighter and more precise delineation of AVM target volumes could be achieved by using triple-MRA for radiosurgery targeting. However, further research is required to ascertain the impact this may have in obliteration rates and side effects. Show less
