Neuroimaging encompases both structural imaging of the brain and spine and the variety of advanced neuroimaging techniques to evaluate neurological disease and manage treatment. Our department has strong neuroradiological expertise in clinical practice and neuroscience research, with emphasis on stroke, small vessel disease, neurodegenerative disorders and demyelination. Our neuroradiologists are part of a multidisciplinary neuroscience team, and provide high resolution imaging and functional techniques that improve patient care in Hong Kong. An important focus of our current research is directed towards the clinical translation of brain volumetry, and the exploration of novel MRI biomarkers in dementias. Additionally we leverage our computational expertise towards the elucidation of mechanisms of cognition in both community dwellers and patient populations.

• Early onset dementia registry
• Screening for elderly cognitive disorders
• Alzheimer’s dementia registry

Arterial spin labeling depicts loss of “light bulb sign” in a patient with Alzheimer’s Disease

• Multiple sclerosis registry
  
• Quantification of brain iron deposition in Parkinson’s Disease
  
  

  Quantitative susceptibility map in a patient with Parkinson’s Disease

• Imaging, Clinical and Other Biomarkers in Small vessel disease (multicenter collaboration with other hospitals in China)
• Validation of automated brain volumetry to assist clinical diagnosis
  
  

  Automated brain volumetry using AccuBrain®

• A randomised, single blind, controlled trial of electro acupuncture for the treatment of symptomatic gallstone diseases

Magnetic resonance perfusion for differentiating low-grade from high-grade gliomas at first presentation

Abrigo JM, Fountain DM, Provenzale JM, Law EK, Kwong JS, Hart MG, Tam WWS. Cochrane Database Syst Rev. 2018 Jan 22;1:CD011551. doi: 10.1002/14651858.CD011551.pub2.

BACKGROUND: Gliomas are the most common primary brain tumour. They are graded using the WHO classification system, with Grade II-IV astrocytomas, oligodendrogliomas and oligoastrocytomas. Low-grade gliomas (LGGs) are WHO Grade II infiltrative brain tumours that typically appear solid and non-enhancing on magnetic resonance imaging (MRI) scans. People with LGG often have little or no neurologic deficit, so may opt for a watch-and-wait-approach over surgical resection, radiotherapy or both, as surgery can result in early neurologic disability. Occasionally, high-grade gliomas (HGGs, WHO Grade III and IV) may have the same MRI appearance as LGGs. Taking a watch-and-wait approach could be detrimental for the patient if the tumour progresses quickly. Advanced imaging techniques are increasingly used in clinical practice to predict the grade of the tumour and to aid clinical decision of when to intervene surgically. One such advanced imaging technique is magnetic resonance (MR) perfusion, which detects abnormal haemodynamic changes related to increased angiogenesis and vascular permeability, or “leakiness” that occur with aggressive tumour histology. These are reflected by changes in cerebral blood volume (CBV) expressed as rCBV (ratio of tumoural CBV to normal appearing white matter CBV) and permeability, measured by Ktrans.

OBJECTIVES: To determine the diagnostic test accuracy of MR perfusion for identifying patients with primary solid and non-enhancing LGGs (WHO Grade II) at first presentation in children and adults. In performing the quantitative analysis for this review, patients with LGGs were considered disease positive while patients with HGGs were considered disease negative.To determine what clinical features and methodological features affect the accuracy of MR perfusion.

SEARCH METHODS: Our search strategy used two concepts: (1) glioma and the various histologies of interest, and (2) MR perfusion. We used structured search strategies appropriate for each database searched, which included: MEDLINE (Ovid SP), Embase (Ovid SP), and Web of Science Core Collection (Science Citation Index Expanded and Conference Proceedings Citation Index). The most recent search for this review was run on 9 November 2016.We also identified ‘grey literature’ from online records of conference proceedings from the American College of Radiology, European Society of Radiology, American Society of Neuroradiology and European Society of Neuroradiology in the last 20 years.

SELECTION CRITERIA: The titles and abstracts from the search results were screened to obtain full-text articles for inclusion or exclusion. We contacted authors to clarify or obtain missing/unpublished data.We included cross-sectional studies that performed dynamic susceptibility (DSC) or dynamic contrast-enhanced (DCE) MR perfusion or both of untreated LGGs and HGGs, and where rCBV and/or Ktrans values were reported. We selected participants with solid and non-enhancing gliomas who underwent MR perfusion within two months prior to histological confirmation. We excluded studies on participants who received radiation or chemotherapy before MR perfusion, or those without histologic confirmation.

DATA COLLECTION AND ANALYSIS: Two review authors extracted information on study characteristics and data, and assessed the methodological quality using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We present a summary of the study characteristics and QUADAS-2 results, and rate studies as good quality when they have low risk of bias in the domains of reference standard of tissue diagnosis and flow and timing between MR perfusion and tissue diagnosis.In the quantitative analysis, LGGs were considered disease positive, while HGGs were disease negative. The sensitivity refers to the proportion of LGGs detected by MR perfusion, and specificity as the proportion of detected HGGs. We constructed two-by-two tables with true positives and false negatives as the number of correctly and incorrectly diagnosed LGG, respectively, while true negatives and false positives are the number of correctly and incorrectly diagnosed HGG, respectively.Meta-analysis was performed on studies with two-by-two tables, with further sensitivity analysis using good quality studies. Limited data precluded regression analysis to explore heterogeneity but subgroup analysis was performed on tumour histology groups.

MAIN RESULTS: Seven studies with small sample sizes (4 to 48) met our inclusion criteria. These were mostly conducted in university hospitals and mostly recruited adult patients. All studies performed DSC MR perfusion and described heterogeneous acquisition and post-processing methods. Only one study performed DCE MR perfusion, precluding quantitative analysis.Using patient-level data allowed selection of individual participants relevant to the review, with generally low risks of bias for the participant selection, reference standard and flow and timing domains. Most studies did not use a pre-specified threshold, which was considered a significant source of bias, however this did not affect quantitative analysis as we adopted a common rCBV threshold of 1.75 for the review. Concerns regarding applicability were low.From published and unpublished data, 115 participants were selected and included in the meta-analysis. Average rCBV (range) of 83 LGGs and 32 HGGs were 1.29 (0.01 to 5.10) and 1.89 (0.30 to 6.51), respectively. Using the widely accepted rCBV threshold of <1.75 to differentiate LGG from HGG, the summary sensitivity/specificity estimates were 0.83 (95% CI 0.66 to 0.93)/0.48 (95% CI 0.09 to 0.90). Sensitivity analysis using five good quality studies yielded sensitivity/specificity of 0.80 (95% CI 0.61 to 0.91)/0.67 (95% CI 0.07 to 0.98). Subgroup analysis for tumour histology showed sensitivity/specificity of 0.92 (95% CI 0.55 to 0.99)/0.42 (95% CI 0.02 to 0.95) in astrocytomas (6 studies, 55 participants) and 0.77 (95% CI 0.46 to 0.93)/0.53 (95% CI 0.14 to 0.88) in oligodendrogliomas+oligoastrocytomas (6 studies, 56 participants). Data were too sparse to investigate any differences across subgroups.

AUTHORS’ CONCLUSIONS: The limited available evidence precludes reliable estimation of the performance of DSC MR perfusion-derived rCBV for the identification of grade in untreated solid and non-enhancing LGG from that of HGG. Pooled data yielded a wide range of estimates for both sensitivity (range 66% to 93% for detection of LGGs) and specificity (range 9% to 90% for detection of HGGs). Other clinical and methodological features affecting accuracy of the technique could not be determined from the limited data. A larger sample size of both LGG and HGG, preferably using a standardised scanning approach and with an updated reference standard incorporating molecular profiles, is required for a definite conclusion.

Correlation of non-vitamin K antagonist oral anticoagulant exposure and cerebral microbleeds in Chinese patients with atrial fibrillation

Soo Y, Abrigo J, Leung KT, Liu W, Lam B, Tsang SF, Ip V, Ma K, Ip B, Ma SH, Fan F, Chu W, Wong L, Mok V, Leung TW. J Neurol Neurosurg Psychiatry. 2018 Mar 29. doi: 10.1136/jnnp-2017-317151.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are radiological markers which predict future intracerebral haemorrhage. Researchers are exploring how CMBs can guide anticoagulation decisions in atrial fibrillation (AF). The purpose of this study is to evaluate the correlation of non-vitamin K antagonist oral anticoagulants (NOAC) exposure and prevalence of CMBs in Chinese patients with AF.

METHODS: We prospectively recruited Chinese patients with AF on NOAC therapy of ≥30 days for 3T MRI brain for evaluation of CMBs and white matter hyperintensities. Patients with AF without prior exposure to oral anticoagulation were recruited as control group.

RESULTS: A total of 282 patients were recruited, including 124 patients in NOAC group and 158 patients in control group. Mean duration of NOAC exposure was 723.8±500.3 days. CMBs were observed in 103 (36.5%) patients. No significant correlation was observed between duration of NOAC exposure and quantity of CMBs. After adjusting for confounding factors (ie, age, hypertension, labile hypertension, stroke history and white matter scores), previous intracerebral haemorrhage was predictive of CMBs (OR 15.28, 95% CI 1.81 to 129.16), particularly lobar CMBs (OR 5.37, 95% CI 1.27 to 22.6). While white matter score was predictive of mixed lobar CMBs (OR 1.65, 95% CI 1.1 to 2.5), both exposure and duration of NOAC use were not predictive of presence of CMBs.

CONCLUSIONS: In Chinese patients with AF, duration of NOAC exposure did not correlate with prevalence and burden of CMBs. Further studies with follow-up MRI are needed to determine if long-term NOAC therapy can lead to development of new CMBs.

Enlarged perivascular spaces and cognition: a meta-analysis of five population-based studies

Hilal S, Tan CS, Adams HHH, Habes M, Mok V, Venketasubramanian N, Hofer E, Ikram MK, Abrigo J, Vernooji MW, Chen CPLH, Hosten N, Völzke H, Grabe HJ, Schmidt R, Ikram MA. Neurology (accepted)

Qualitative Evaluation of a High-Resolution 3D Multi-Sequence Intracranial Vessel Wall Protocol at 3 Tesla MRI

Dieleman N, Yang W, van der Kolk AG, Abrigo J, Lee KL, Chu WC, Zwanenburg J, Siero JC, Wong KS, Hendrikse J, Chen FX. PLoS One. 2016 Aug 17;11(8):e0160781. doi: 10.1371/journal.pone.0160781.

Abstract

BACKGROUND and PURPOSE: Intracranial vessel wall imaging using MRI has great potential as a clinical method for assessing intracranial atherosclerosis. The purpose of the current study was to compare three 3T MRI vessel wall sequences with different contrast weightings (T1w, PD, T2w) and dedicated sagittal orientation perpendicular to the middle cerebral artery, to the reconstructed sagittal image from a transverse 3D T1w volumetric isotropically reconstructed turbo spin-echo acquisition (VIRTA), and provide a clinical recommendation.

MATERIALS AND METHODS: The above-mentioned sequences were acquired in 10 consecutive Chinese ischemic stroke or TIA patients (age: 68 years, sex: 4 females) with angiographic-confirmed MCA stenosis at 3T. Institutional review board approval was obtained. Two raters qualitatively scored all images on overall image quality, presence of artifacts, and visibility of plaques. Data were compared using Repeated measures ANOVA and Sidak’s adjusted post hoc tests.

RESULTS: All sequences except the T2w sequence were able to depict the walls of the large vessels of the Circle of Willis (p<0.05). T1w sagittal oblique VIRTA showed significantly more artifacts (p<0.01). Peripherally located plaques were sometimes missed on the sagittal sequences, but could be appreciated on the transverse T1w VIRTA.

CONCLUSIONS: With the 3T multi-sequence vessel wall protocol we were able to assess the intracranial plaque with two different image contrast weightings. The sequence of preference to include in a clinical protocol would be the transverse 3D T1w VIRTA based on absence of artifacts, larger coverage including the whole Circle of Willis, and excellent lesion depiction.

Magnetic Resonance Imaging of Plaque Morphology, Burden, and Distribution in Patients With Symptomatic Middle Cerebral Artery Stenosis

Dieleman N, Yang W, Abrigo JM, Chu WC, van der Kolk AG, Siero JC, Wong KS, Hendrikse J, Chen XY. Stroke. 2016 Jul;47(7):1797-802. doi: 10.1161/STROKEAHA.116.013007.

Abstract

BACKGROUND AND PURPOSE: Intracranial atherosclerosis is a major cause of ischemic stroke worldwide. Intracranial vessel wall imaging is an upcoming field of interest to assess intracranial atherosclerosis. In this study, we investigated total intracranial plaque burden in patients with symptomatic middle cerebral artery stenosis, assessed plaque morphological features, and compared features of symptomatic and asymptomatic lesions using a 3T vessel wall sequence.

METHODS: Nineteen consecutive Chinese patients with ischemic stroke and transient ischemic attack (mean age: 67 years; 7 females) with a middle cerebral artery stenosis were scanned at 3T magnetic resonance imaging; the protocol included a time-of-flight magnetic resonance angiography and the T1-weighted volumetric isotropically reconstructed turbo spin echo acquisition sequence before and after (83%) contrast administration. Chi-square tests were used to assess associations between different plaque features. Statistical significance was set at P<0.05.

RESULTS: Vessel wall lesions were identified in 18 patients (95%), totaling 57 lesions in 494 segments (12% of segments). Lesions were located primarily in the anterior circulation (82%). Eccentric lesions were associated with a focal thickening pattern and concentric lesions with a diffuse thickening pattern (P<0.001). When differentiating between asymptomatic and symptomatic lesions, an association (P<0.05) was found between eccentricity and asymptomatic lesions, but not for enhancement or a specific thickening pattern. Symptomatic lesions did not have any specific morphological features.

CONCLUSIONS: Our results lead to a 2-fold conclusion: (1) The classification system of both thickening pattern and distribution of the lesion can be simplified by using distribution pattern only and (2) differentiation between symptomatic and asymptomatic atherosclerotic lesions was possible using intracranial vessel wall imaging.

Other Projects

• Risk of Intracerebral Haemorrhage in Patients Taking Oral Anticoagulant for Atrial Fibrillation with Cerebral Microbleeds. A Prospective Study in Warfarin
• Vessel wall imaging of atherosclerotic plaques of the middle cerebral artery