Henry Ka-Fung Mak

Evaluation of carotid stenosis using CT angiography in the initial evaluation of stroke and TIA

Background: Imaging of the carotid arteries is important for the evaluation of patients with ischemic stroke or TIA. CT angiography (CTA) of the head and neck is readily available and can be part of the routine imaging of stroke patients. To evaluate the accuracy of CTA, the authors compared the degree of stenosis found using CTA with digital subtraction angiography (DSA) in consecutive patients during a 3-year period. Methods: The authors included all patients with interpretable CTA and DSA of the cervical carotid arteries from April 2000 to November 2002 at a single academic medical center. This yielded a total of 81 vessels. Stenosis on CTA of the internal carotid artery was measured in the axial plane at the point of maximum stenosis and referenced to the distal cervical internal carotid by two blinded readers. Two blinded readers measured stenosis from the DSA using the North American Symptomatic Carotid Endarterectomy Trial method. Results: Using a 70% cutoff value for stenosis, CTA and DSA were in agreement in 78 of 81 (96%; 95% CI, 90 to 99%) vessels. CTA was 100% sensitive (n = 5) and 63% specific (95% CI, 25 to 88%), and the negative predictive value of a CTA demonstrating <70% stenosis was 100% (n = 73). Conclusions: In this consecutive series of patients with CT angiography of the neck and digital subtraction angiography, the authors found that CT angiography has a high sensitivity and high negative predictive value for carotid disease. CT angiography appears to be an excellent screening test for internal carotid artery stenosis, and the authors advocate its use for the initial imaging of patients with suspected stroke or TIA.

C-Reactive Protein Is Associated With Obstructive Sleep Apnea Independent of Visceral Obesity

BACKGROUND Obstructive sleep apnea (OSA) is associated with adverse cardiovascular outcomes. C-reactive protein (CRP) predicts atherosclerotic complications. Our study evaluates whether OSA is associated with an elevated CRP level, after elimination of known confounders including visceral obesity. METHODS Men without significant chronic medical illness, regular medications, or illness in the preceding 4 weeks were enrolled. Subjects with morbid obesity, newly detected high BP, or fasting glucose were excluded. They underwent polysomnography and MRI of abdomen to quantify visceral fat volume. High-sensitivity CRP levels were measured. RESULTS 111 men with mean body mass index (BMI) 26.3 +/- 3.8 kg/m(2) were evaluated. After adjustment for age, smoking, BMI, waist circumference, and sleep efficiency, CRP correlated positively with the apnea-hypopnea index (AHI) [r = 0.35, p < 0.001], duration of O(2) saturation < 90% (r = 0.29, p = 0.002), and arousal index (r = 0.32, p = 0.001), and it correlated negatively with minimal O(2) saturation (r = -0.29, p = 0.002). These correlations were consistent when adjustment was made for MRI visceral fat volume instead of waist circumference. In the regression model, significant predictors of CRP included AHI, waist circumference, and triglycerides (adjusted R(2), 0.33, p = 0.001, p = 0.002, p = 0.018, respectively). Among the 111 subjects, 32 subjects with no or mild OSA (AHI < 15 events/h) were matched with 32 subjects with moderate-to-severe OSA (AHI > or = 15 events/h) in MRI visceral fat volume. CRP was higher in subjects with moderate-to-severe OSA (median, 1.32; 0.45 to 2.34 mg/L) when compared to subjects with no or mild OSA (median, 0.54; 0.25 to 0.89 mg/L; p = 0.001). CONCLUSIONS In healthy middle-aged men, elevated CRP level is associated with OSA independent of visceral obesity.

The default mode network is disrupted in parkinson's disease with visual hallucinations

Background: Visual hallucinations (VH) are one of the most striking nonmotor symptoms in Parkinsons disease (PD), and predict dementia and mortality. Aberrant default mode network (DMN) is associated with other psychoses. Here, we tested the hypothesis that DMN dysfunction contributes to VH in PD. Methods: Resting state functional data was acquired from individuals with PD with VH (PDVH) and without VH (PDnonVH), matched for levodopa drug equivalent dose, and a healthy control group (HC). Independent component analysis was used to investigate group differences in functional connectivity within the DMN. In addition, we investigated whether the functional changes associated with hallucinations were accompanied by differences in cortical thickness. Results: There were no group differences in cortical thickness but functional coactivation within components of the DMN was significantly lower in both PDVH and PDnonVH groups compared to HC. Functional coactivation within the DMN was found to be greater in PDVH group relative to PDnonVH group. Conclusion: Our study demonstrates, for the first time that, within a functionally abnormal DMN in PD, relatively higher “connectivity” is associated with VH. We postulate that aberrant connectivity in a large scale network affects sensory information processing and perception, and contributes to “positive” symptom generation in PD. Hum Brain Mapp 35:5658–5666, 2014.

Hypodensity of >1/3 Middle Cerebral Artery Territory Versus Alberta Stroke Programme Early CT Score (ASPECTS) Comparison of Two Methods of Quantitative Evaluation of Early CT Changes in Hyperacute Ischemic Stroke in the Community Setting

Background— The one third middle cerebral artery territory (⅓ MCA) method and the Alberta Stroke Program Early CT Score (ASPECTS) were used to detect significant early ischemic changes (EIC) on CT brain of acute stroke patients. We sought to compare the reliability of the 2 methods in routine clinical practice. Methods— Eighty consecutive patients admitted to a community hospital in Hong Kong with suspected acute ischemic stroke and a CT brain scan performed within 6 hours of symptom onset were included. Five blinded observers (1 neurologist, 2 general radiologists, and 2 neuroradiologists) independently evaluated the scans, using the ATLANTIS/CT Summit criteria for >⅓ MCA involvement, and ASPECTS ≤7. Kappa statistics were used to determine interobserver agreement. Results— Significant EIC were present in 11.4% of the scans with the ⅓ MCA method, and 19.4% with ASPECTS. For >⅓ MCA involvement, all observers agreed in 57 cases (71%), with moderate interobserver agreement (&kgr;=0.49). For ASPECTS ≤7, all observers agreed in 34 cases (42%), with fair interobserver agreement (&kgr;=0.34). After prevalence and bias adjustments, substantial (prevalence-adjusted bias-adjusted &kgr; [PABAK]=0.74) and moderate (PABAK=0.44) agreements were found for the ⅓ MCA method and ASPECTS respectively. Conclusions— The ⅓ MCA method was more reliable in detecting significant EIC on CT brain within 6 hours of stroke onset in routine clinical practice, whereas ASPECTS was able to detect significant EIC in a higher proportion of these early scans.

Pediatric 64-MDCT Coronary Angiography With ECG-Modulated Tube Current: Radiation Dose and Cancer Risk

OBJECTIVE The purpose of our study was to measure the radiation dose from ECG-gated CT coronary angiography in children and to estimate the cancer risk associated with the radiation dose. MATERIALS AND METHODS Organ doses were measured with a 5-year-old pediatric phantom and thermoluminescent dosimeters on a 64-MDCT scanner. Four retrospectively ECG-gated CT coronary angiography protocols with four simulated heart rates and the corresponding pitches were studied. The lifetime attributable risk of cancer incidence was estimated for children in the United States and Hong Kong according to the National Academies Biologic Effects of Ionizing Radiation VII report. RESULTS The effective doses were 16.45, 12.17, 11.97, and 11.81 mSv for the four protocols, respectively. The corresponding lifetime attributable risks estimated for 5-year-old U.S. boys and girls were 0.14%-0.20% and 0.43%-0.60%, respectively, and for 5-year-old Hong Kong boys and girls were 0.22%-0.33% and 0.61%-0.85%. In relation to the total cancer incidence (baseline cancer incidence plus lifetime attributable risk), lifetime attributable risk from radiation exposure contributed up to 0.99% and 3.51% for Hong Kong boys and girls and up to 0.46% and 1.57% for U.S. boys and girls. CONCLUSION Our results suggest that radiation dose and cancer risk of CT coronary angiography to pediatric patients are not negligible, more so in Hong Kong children than in U.S. children. Therefore, these examinations should be well justified clinically.

Efficacy of voxel-based morphometry with DARTEL and standard registration as imaging biomarkers in alzheimer's disease patients and cognitively normal older adults at 3.0 tesla MR imaging

Quantitative MRI of the hippocampus has been increasingly employed as a biomarker in Alzheimers disease (AD). We compare voxel-based morphometry (VBM) standard and DARTEL registration with manual hippocampal volumetry in AD patients and cognitively normal older adults. Participants were 20 cognitively normal elderly subjects and 19 AD patients who met the criteria of probable AD according to NINCDS-ADRDA. Bilateral manual hippocampal volumetry was conducted alongside VBM of hippocampal regions-of-interest (ROIs) generated with standard and DARTEL registration using hippocampal masks and total intracranial volume normalization. All normalized hippocampal measurements showed significant reduction (20–30%; p < 0.001) in AD compared to controls. Logistic regression analysis also showed significant effects (odds ratios ranged from 88.2% to 94.0%) of all normalized measurements in predicting AD incidence after adjusting for age, gender, and education. The overall prediction accuracies of manual RH and LH volumes, standard RH-ROI and LH-ROI VBM, DARTEL RH-ROI, and LH-ROI VBM were 87.2%, 84.6%, 87.2%, 76.9%, 87.2%, and 87.2%, respectively. As imaging biomarkers, VBM with DARTEL and standard registration have similarly high efficacies as manual hippocampal volumetry in discriminating AD from cognitively normal elderly adults.

Quantitative Assessment of Cerebral Hemodynamic Parameters by QUASAR Arterial Spin Labeling in Alzheimer's Disease and Cognitively Normal Elderly Adults at 3-Tesla

QUASAR arterial spin labeling (ASL) was used to investigate the role of vascular impairment in Alzheimers disease (AD). We hypothesized that the hemodynamic parameters monitoring cerebrovascular integrity, i.e., cerebral blood flow (CBF), arterial blood volume (aBV), and arterial transit time (aTT), would be affected. 13 AD patients and 15 healthy control (HC) subjects underwent 3T MRI scanning. Two separate blood flow acquisitions were obtained with 1 slice overlap for whole brain coverage. CBF, aBV, and aTT maps were calculated using in-house software. Preprocessing and statistical analyses were performed on SPM5. Region-of-interest (ROI) studies of ten selected cerebral regions were also conducted. There were significant differences in mini mental status exam (MMSE) (AD: 16.3 ± 4.55, HC: 28.5 ± 2.00) and Alzheimers disease assessment scale-cognitive subscale (ADAS-cog) scores (AD: 25.25 ± 9.64, HC: 5.51 ± 2.62) between the 2 groups (p < 0.001) but none in age (p = 0.068). CBF decreased significantly (p < 0.01) in AD compared to controls in the right middle cingulate, left cuneus, left inferior and middle frontal, right superior frontal, left inferior parietal, and right supramarginal gyri. ROI studies confirmed significant hemodynamic impairments in AD compared to HC (p < 0.05): CBF in middle and posterior cingulate, aBV in left superior temporal, right inferior parietal, and posterior cingulate, and aTT in left inferior frontal and middle cingulate gyri. CBF correlated positively while aTT correlated negatively to MMSE, and vice versa for ADAS-cog. Using QUASAR ASL, we found patterns of regional hemodynamic impairment typical of moderate AD, suggesting underlying vascular abnormality. As potential biomarkers, these hemodynamic parameters could differentiate patients from volunteers, and possibly indicate the conversion from healthy aging to mild cognitive impairment to AD.

Nasopharyngeal carcinoma: relationship between 18F-FDG PET-CT maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis and TNM classification.

PurposeWe aimed to evaluate the relationships between primary tumour; maximum standardized uptake value (SUVmax), metabolic tumour volume (TV) and total lesion glycolysis (TLG) and tumour-node metastases (TNM) classification in nasopharyngeal carcinoma (NPC) patients. MethodsFluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography scans of 57 consecutive newly diagnosed NPC patients (age range, 15–80 years) were retrospectively reviewed. SUVmax, TV and TLG were recorded. Two-tailed Spearmans correlation was used to analyse the relationships between the metabolic parameters and the TNM staging system. ResultsPositive correlations were observed between SUVmax (P<0.001, R=0.516), TV (P<0.001, R=0.504) and TLG (P<0.001, R=0.620) and T-stage, and both TV and SUVmax were independent variables that significantly affected T-stage (P<0.001, adjusted R2=0.370). No other significant correlations were found between the metabolic parameters and TNM classification system. ConclusionThe metabolic parameters derived from fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography were positively correlated with T-stage in primary NPC. Our findings may suggest a complementary role of these parameters to TNM staging in prognostication of NPC patients.

Computed Tomography Evaluation of Intracranial Atherosclerosis in Chinese Patients with Transient Ischemic Attack or Minor Ischemic Stroke—Its Distribution and Association with Vascular Risk Factors

OBJECTIVES Intracranial atherosclerosis has been suggested to be common in Asians. We apply a semi-quantitative CT scoring system to evaluate the degree of intracranial atherosclerotic calcification and determine its distribution, severity, and the associated risk factors. The clinical outcome of these patients after a 3-year follow-up was also evaluated. METHODS Sixty consecutive patients diagnosed clinically to have either a transient ischemic attack (TIA) or minor ischemic stroke and underwent early computed tomographic angiography (CTA) were included into the prospective study. Two radiologists evaluated the axial CTA images for any calcification in the precavernous, cavernous and postcavernous segments of intracranial internal carotid artery (ICA), anterior, middle, and posterior cerebral as well as vertebrobasilar arteries, based on a standard CT scoring system for extent (0-4) and thickness (0-4). The composite CT score for extent and thickness of these vascular segments or vessels were recorded for all patients. The worst site (highest composite score) was chosen as the marker of the degree of intracranial atherosclerosis of each patient. The patients were then classified into mild, moderate, and severe groups, according to a composite CT score of 0-2, 3-5, and 6-8, respectively. These findings were gathered with clinical parameters and outcome after a 3-year follow-up period and corresponding statistical analyses were conducted. RESULTS The most severely affected vessel was found to be intracranial internal carotid arteries, and severe, moderate, and mild atherosclerosis were present in 16 (26.67%), 30 (50%), and 14 (23.33%) patients, respectively. Using multiple logistic regression analysis, diabetes mellitus (odds ratio = 10.6, P value = .004), and age (odds ratio = 1.07, P value = .02) were found to be significant risk factors for severe intracranial atherosclerosis. Two patients in the severe group, 3 patients in the moderate group, and 1 patient in the mild group were found to have stroke or TIA after a 3-year follow-up, but there was no significant difference among the 3 groups. CONCLUSION Significant intracranial atherosclerosis as determined by severe CT calcification was common in a cohort of Chinese patients with TIA and minor stroke. Age and diabetes mellitus were independent significant risk factors, and this CT calcification score might serve as an early indicator of intracranial atherosclerotic disease.

Multimodal MRI of the hippocampus in Parkinson’s disease with visual hallucinations

Visual hallucinations carry poor prognosis in Parkinson’s disease. Here we tested the hypothesis that the hippocampus and visuospatial memory impairment play a central role in the pathology of PD with visual hallucinations. Multimodal magnetic resonance imaging of the brain was carried out in 12 people with PD and visual hallucinations; 15 PD individuals without hallucinations; and 14 healthy controls. Age, gender, cognitive ability, and education level were matched across the three groups. PD patients were taking dopaminergic medication. Hippocampal volume, shape, mean diffusivity (MD), and functional connectivity within the whole brain were examined. Visuospatial memory was compared between groups, and correlations with hippocampal MD, functional connectivity, and the severity of hallucinations were explored. There were no macrostructural differences across groups, but individuals with hallucinations had higher diffusivity in posterior hippocampus than the other two groups. Visuospatial memory was poorer in both PD groups compared to controls, and was correlated with hallucinations. Finally, hippocampal functional connectivity in the visual cortices was lower in those with hallucinations than other groups, and this correlated with visuospatial memory impairment. In contrast, functional connectivity between the hippocampus and default mode network regions and frontal regions was greater in the PD hallucinators compared to other groups. We suggest that hippocampal pathology, which disrupts visuospatial memory, makes a key contribution to visual hallucinations in PD. These findings may pave the way for future studies of imaging biomarkers to measure treatment response in those with PD who are most at risk of poor outcomes.