Piotr A. Wielopolski

Prevalence and risk factors of cerebral microbleeds: The Rotterdam Scan Study

Background: Cerebral microbleeds are focal deposits of hemosiderin that can be visualized with MRI. Little is known on their prevalence in the general population and on their etiology. It has been suggested that, in analogy to spontaneous intracranial hemorrhage, the etiology of microbleeds differs according to their location in the brain, with lobar microbleeds being caused by cerebral amyloid angiopathy and deep or infratentorial microbleeds resulting from hypertension and atherosclerosis. We investigated the prevalence of and risk factors for microbleeds in the general population aged 60 years and older. Methods: This study is based on 1,062 persons (mean age 69.6 years) from the population-based Rotterdam Scan Study. MRI was performed at 1.5 T and included a sequence optimized to increase the conspicuity of microbleeds. We assessed the relation of APOE genotype, cardiovascular risk factors, and markers of small vessel disease to the presence and location of microbleeds with multiple logistic regression. Results: Overall prevalence of cerebral microbleeds was high and increased with age from 17.8% in persons aged 60-69 years to 38.3% in those over 80 years. APOE ε4 carriers had significantly more often strictly lobar microbleeds than noncarriers. In contrast, cardiovascular risk factors and presence of lacunar infarcts and white matter lesions were associated with microbleeds in a deep or infratentorial location but not in a lobar location. Conclusion: The prevalence of cerebral microbleeds is high. Our data support the hypothesis that strictly lobar microbleeds are related to cerebral amyloid angiopathy, whereas microbleeds in a deep or infratentorial location result from hypertensive or atherosclerotic microangiopathy.

Comparison of contrast-enhanced magnetic resonance angiography and conventional pulmonary angiography for the diagnosis of pulmonary embolism : a prospective study

BACKGROUND Diagnostic strategies for pulmonary embolism are complex and consist of non-invasive diagnostic tests done to avoid conventional pulmonary angiography as much as possible. We aimed to assess the diagnostic accuracy of magnetic resonance angiography (MRA) for the diagnosis of pulmonary embolism, using conventional pulmonary angiography as a reference method. METHODS In a prospective study, we enrolled 141 patients with suspected pulmonary embolism and an abnormal perfusion scan. Patients underwent MRA before conventional pulmonary angiography. Two reviewers, masked with respect to the results of conventional pulmonary angiography, assessed MRA images independently. Statistical analyses used chi(2) and 95% CI. FINDINGS MRA was contraindicated in 13 patients (9%), and images were not interpretable in eight (6%). MRA was done in two patients in whom conventional pulmonary angiography was contraindicated. Thus, MRA and conventional pulmonary angiography results were available in 118 patients (84%). Prevalence of pulmonary embolism was 30%. Images were read independently in 115 patients, and agreement obtained in 105 (91%), kappa=0.75. MRA identified 27 of 35 patients with proven pulmonary embolism (sensitivity 77%, 95% CI 61-90). Sensitivity of MRA for isolated subsegmental, segmental, and central or lobar pulmonary embolism was 40%, 84%, and 100%, respectively (p<0.01 for isolated subsegmental vs segmental or larger pulmonary embolism). However, subgroups contained small numbers. MRA identified pulmonary embolism in two patients with normal angiogram (98%, 92-100). INTERPRETATION MRA is sensitive and specific for segmental or larger pulmonary embolism. Results are similar to those obtained with helical computed tomography, but MRA has safer contrast agents and does not involve ionising radiation. MRA could become part of the diagnostic strategy for pulmonary embolism.

Fiber density asymmetry of the arcuate fasciculus in relation to functional hemispheric language lateralization in both right- and left-handed healthy subjects: A combined fMRI and DTI study

Previously reported leftward asymmetry in language-related gray and white matter areas of the brain has been proposed as a structural correlate of left-sided functional hemispheric language lateralization. However, structural asymmetry in non-left-sided functional language lateralization has as yet not been studied. Furthermore, the neuroanatomical basis of the reported volumetric white matter asymmetry is not fully understood. In 20 healthy volunteers, including 13 left-handers, we performed functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). We studied the relative fiber density (RFD) of the arcuate fasciculus (AF), using DT-tractography, in relation to functional hemispheric language lateralization. Hemispheric language lateralization was right-sided in five left-handed individuals. We demonstrated an overall significant leftward asymmetry in RFD of the AF, irrespective of handedness or functional language lateralization. Furthermore, in right-handers, the degree of structural asymmetry was found to be correlated with the degree of functional lateralization. We conclude that structural asymmetry in the AF does not seem to reflect functional hemispheric language lateralization, as has been proposed previously. Our findings suggest that the previously reported white matter asymmetry may be explained by a structural asymmetry in the arcuate fasciculus. These findings have important implications for the understanding of the functional and structural lateralization of brain regions as well as for the clinical evaluation of language function.

White Matter Microstructural Integrity and Cognitive Function in a General Elderly Population

CONTEXT The role of macrostructural white matter changes, such as atrophy and white matter lesions, in cognitive decline is increasingly being recognized. However, in the elderly population, these macrostructural changes do not account for all variability in cognition. Measures reflecting white matter microstructural integrity may provide additional information to investigate the relation between white matter changes and cognition. OBJECTIVE To study the relation between white matter integrity and cognition in the general elderly population, using diffusion tensor imaging and taking into account macrostructural white matter changes. DESIGN Cross-sectional population-based study. SETTING A general community in the Netherlands. PARTICIPANTS A population-based sample of 860 persons, older than 60 years, free of dementia. We performed multisequence magnetic resonance imaging, which included diffusion tensor imaging, and extensive neuropsychological testing. Fractional anisotropy, mean diffusivity, and directional diffusivities were measured globally in white matter lesions and normal-appearing white matter. MAIN OUTCOME MEASURES Performance on neuropsychological tests in the following cognitive domains: memory, executive function, information processing speed, global cognition, and motor speed. RESULTS Regardless of macrostructural white matter changes, a higher mean diffusivity or higher axial and radial diffusivities within white matter lesions or normal-appearing white matter were related to worse performance on tasks assessing information processing speed and global cognition. In addition, diffusivity within white matter lesions related to memory, while in normal-appearing white matter, it furthermore related to executive function. Lower mean fractional anisotropy in white matter lesions or normal-appearing white matter related to worse information processing speed and motor speed. CONCLUSIONS Microstructural integrity of both white matter lesions and normal-appearing white matter is associated with cognitive function, regardless of white matter atrophy and white matter lesion volume. This suggests that measuring white matter integrity has added value beyond macrostructural assessment of white matter changes to study the relation between white matter and cognition.

Cerebral microbleeds: Accelerated 3D T2*-weighted GRE MR imaging versus conventional 2D T2*-weighted GRE MR imaging for detection

The purpose of this study was to prospectively compare high-spatial-resolution accelerated three-dimensional (3D) T2*-weighted gradient-recalled-echo (GRE) magnetic resonance (MR) images with conventional two-dimensional (2D) T2*-weighted GRE MR images for the depiction of cerebral microbleeds. After obtaining institutional review board approval and informed consent, 200 elderly participants (age range, 69.7-96.7 years; 108 [54%] women) were imaged at 1.5 T by using both sequences. Presence, number, and location of microbleeds were recorded for both sequences, and differences were tested by using McNemar and signed rank tests. Cerebral microbleeds were detected in significantly more participants on 3D T2*-weighted GRE images (35.5%) than on 2D T2*-weighted GRE images (21.0%; P < .001). Furthermore, in persons with microbleeds visualized on both image sets, significantly more microbleeds (P < .001) were seen on 3D images than on 2D images. For both sequences, the proportion of participants with a microbleed in a lobar (cortical gray and subcortical white matter), deep, or infratentorial location was similar. In conclusion, accelerated 3D T2*-weighted GRE images depict more microbleeds than do conventional 2D T2*-weighted GRE images.

Effects of iron oxide incorporation for long term cell tracking on MSC differentiation in vitro and in vivo

Successful cell therapy will depend on the ability to monitor transplanted cells. With cell labeling, it is important to demonstrate efficient long term labeling without deleterious effects on cell phenotype and differentiation capacity. We demonstrate long term (7 weeks) retention of superparamagnetic iron oxide particles (SPIO) by mesenchymal stem cells (MSCs) in vivo, detectable by MRI. In vitro, multilineage differentiation (osteogenic, chondrogenic and adipogenic) was demonstrated by histological evaluation and molecular analysis in SPIO labeled and unlabeled cells. Gene expression levels were comaparable to unlabeled controls in adipogenic and chondrogenic conditions however not in the osteogenic condition. MSCs seeded into a scaffold for 21 days and implanted subcutaneously into nude mice for 4 weeks, showed profoundly altered phenotypes in SPIO labeled samples compared to implanted unlabeled control scaffolds, indicating chondrogenic differentiation. This study demonstrates long term MSC traceability using SPIO and MRI, uninhibited multilineage MSC differentiation following SPIO labeling, though with subtle but significant phenotypical alterations.

Postconcussion syndrome after minor head injury: Brain activation of working memory and attention

After minor head injury (MHI) postconcussive symptoms (PCS) such as memory and attention deficits frequently occur. It has been hypothesised that PCS are caused by microstructural damage to the brain due to shearing injury, which is not detectable with conventional imaging, and may be responsible for a functional deficit. The purpose of this study was to correlate functional magnetic resonance imaging brain activation of working memory and selective attention with PCS. 21 MHI patients and 12 healthy controls were scanned at 3T. Stimulation paradigms were the n‐back and Counting Stroop tasks to engage working memory and selective attention, respectively. Functional data analysis consisted of random effects group analyses, correlating brain activation patterns with the severity of PCS as evaluated with the Rivermead postconcussion symptoms questionnaire. At minimal working memory load, activation was seen in patients with greater severity of PCS in the working memory network. With an increase of working memory load, increase of activation was more pronounced in patients with greater severity of PCS. At high and increased working memory load, activation associated with the severity of PCS was seen in the posterior parietal area, parahippocampal gyrus, and posterior cingulate gyrus. Activation related to selective attention processing was increased with greater severity of PCS. The increased activity in relation to working memory and attention, and the recruitment of brain areas outside the working memory network at high working memory load, may be considered a reflection of the brains compensatory response to microstructural injury in patients with PCS. Hum Brain Mapp, 2009.

Total cerebral blood flow and total brain perfusion in the general population: The Rotterdam Scan Study

Reduced cerebral perfusion may contribute to the development of cerebrovascular and neurodegenerative diseases. Little is known on cerebral perfusion in the general population, as most measurement techniques are too invasive for application in large groups of healthy individuals. Total cerebral blood flow (tCBF) can be noninvasively measured by magnetic resonance imaging (MRI) but is highly correlated with brain volume. We calculated total brain perfusion by dividing tCBF by brain volume, and we investigated determinants of total brain perfusion in comparison with tCBF. Secondly, we studied whether persons with a low tCBF or low total brain perfusion have a larger volume of white matter lesions (WML). This study is based on 892 persons aged 60 to 91 years from the Rotterdam Study, a population-based cohort study. We performed two-dimensional (2D) phase-contrast MRI for tCBF measurement. Brain volume and WML volume were quantitatively assessed. Cardiovascular determinants were assessed by interview and physical examination. We assessed associations between cardiovascular determinants and flow measures with linear regression models, adjusted for age and sex. Associations between tCBF or total brain perfusion and WML volume were assessed using general linear models. We found that determinants of tCBF and total brain perfusion differed largely due to the large influence of brain volume on tCBF values. Persons with low total brain perfusion had a significantly larger WML volume compared with those with high total brain perfusion. Prospective studies are required to unravel whether hypoperfusion contributes to WML formation or that tissue damage, manifested by WML, leads to brain hypoperfusion.

Can a single‐shot black‐blood T2‐weighted spin‐echo echo‐planar imaging sequence with sensitivity encoding replace the respiratory‐triggered turbo spin‐echo sequence for the liver? an optimization and feasibility study

To optimize and assess the feasibility of a single‐shot black‐blood T2‐weighted spin‐echo echo‐planar imaging (SSBB‐EPI) sequence for MRI of the liver using sensitivity encoding (SENSE), and compare the results with those obtained with a T2‐weighted turbo spin‐echo (TSE) sequence.

Magnetic resonance imaging of the coronary arteries: clinical results from three dimensional evaluation of a respiratory gated technique

BACKGROUND Magnetic resonance coronary angiography is challenging because of the motion of the vessels during cardiac contraction and respiration. Additional challenges are the small calibre of the arteries and their complex three dimensional course. Respiratory gating, turboflash acquisition, and volume rendering techniques may meet the necessary requirements for appropriate visualisation. OBJECTIVE To determine the diagnostic accuracy of respiratory gated magnetic resonance imaging (MRI) for the detection of significant coronary artery stenoses evaluated with three dimensional postprocessing software. METHODS 32 patients referred for elective coronary angiography were studied with a retrospective respiratory gated three dimensional gradient echo MRI technique. Resolution was 1.9 × 1.25 × 2 mm. After manual segmentation three dimensional evaluation was performed with a volume rendering technique. RESULTS Overall 74% (range 50% to 90%) of the proximal and mid coronary artery segments were visualised with an image quality suitable for further analysis. Sensitivity and specificity for the detection of significant stenoses were 50% and 91%, respectively. CONCLUSIONS Volume rendering of respiratory gated MRI techniques allows adequate visualisation of the coronary arteries in patients with a regular breathing pattern. Significant lesions in the major coronary artery branches can be identified with a moderate sensitivity and a high specificity.