Hugo J. Kuijf

Subfields of the hippocampal formation at 7 T MRI: In vivo volumetric assessment

Animal and human autopsy studies suggest that subfields of the hippocampal formation are differentially affected by neuropsychiatric diseases. Therefore, subfield volumes may be more sensitive to effects of disease processes. The few human studies that segmented subfields of the hippocampal formation in vivo either assessed the subfields only in the body of the hippocampus, assessed only three subfields, or did not take the differential angulation of the head of the hippocampus into account. We developed a protocol using 7 Tesla MRI with isotropic voxels to reliably delineate the entorhinal cortex (ERC), subiculum (SUB), CA1, CA2, CA3, dentate gyrus (DG)&CA4 along the full-length of the hippocampus. Fourteen subjects (aged 54-74 years, 2 men and 12 women) were scanned with a 3D turbo spin echo (TSE) sequence with isotropic voxels of 0.7 × 0.7 × 0.7 mm(3) on a 7 T MRI whole body scanner. Based on previous protocols and extensive anatomic atlases, a new protocol for segmentation of subfields of the hippocampal formation was formulated. ERC, SUB, CA1, CA2, CA3 and DG&CA4 were manually segmented twice by one rater from coronal MR images. Good-to-excellent consistency was found for all subfields (Intraclass Correlation Coefficients (ICC) varying from 0.74 to 0.98). Accuracy as measured with the Dice Similarity Index (DSI) was above 0.82 for all subfields, with the exception of the smaller subfield CA3 (0.68-0.70). In conclusion, this study shows that it is possible to delineate the main subfields of the hippocampal formation along its full-length in vivo at 7 T MRI. Our data give evidence that this can be done in a reliable manner. Segmentation of subfields in the full-length of the hippocampus may bolster the study of the etiology neuropsychiatric diseases.

MRBrainS challenge: online evaluation framework for brain image segmentation in 3T MRI scans

Many methods have been proposed for tissue segmentation in brain MRI scans. The multitude of methods proposed complicates the choice of one method above others. We have therefore established the MRBrainS online evaluation framework for evaluating (semi)automatic algorithms that segment gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) on 3T brain MRI scans of elderly subjects (65–80 y). Participants apply their algorithms to the provided data, after which their results are evaluated and ranked. Full manual segmentations of GM, WM, and CSF are available for all scans and used as the reference standard. Five datasets are provided for training and fifteen for testing. The evaluated methods are ranked based on their overall performance to segment GM, WM, and CSF and evaluated using three evaluation metrics (Dice, H95, and AVD) and the results are published on the MRBrainS13 website. We present the results of eleven segmentation algorithms that participated in the MRBrainS13 challenge workshop at MICCAI, where the framework was launched, and three commonly used freeware packages: FreeSurfer, FSL, and SPM. The MRBrainS evaluation framework provides an objective and direct comparison of all evaluated algorithms and can aid in selecting the best performing method for the segmentation goal at hand.

Hippocampal subfield volumes at 7T in early Alzheimer's disease and normal aging

We compared hippocampal subfield and entorhinal cortex (ERC) volumes between patients with mild cognitive impairment (MCI), Alzheimers disease (AD), and controls without cognitive impairment. Additionally, we investigated the relation between age and hippocampal subfields and ERC in controls. We performed ultra-high field 0.7 mm(3) 7Tesla magnetic resonance imaging in 16 patients with amnestic MCI, 9 with AD, and 29 controls. ERC, subiculum, cornu ammonis (CA)1, CA2, CA3, and dentate gyrus (DG)&CA4 were traced on T2-weighted images. Analyses of covariance, adjusted for age, sex, and intracranial volume showed that compared with controls and patients with MCI, patients with AD had significantly smaller ERC, subiculum, CA1, CA3, and DG&CA4 volumes. Trend analyses revealed similar associations between ERC and hippocampal subfields and diagnostic group. Older age was significantly associated with smaller CA1 and DG&CA4 volumes. In conclusion, almost all hippocampal subfields and ERC show volume reductions in patients with AD compared with controls and patients with MCI. Future, larger studies should determine which subfields are affected earliest in the disease process and what mechanisms underlie the volume loss.

Strong Evidence for Pattern Separation in Human Dentate Gyrus.

The hippocampus is proposed to be critical in distinguishing between similar experiences by performing pattern separation computations that create orthogonalized representations for related episodes. Previous neuroimaging studies have provided indirect evidence that the dentate gyrus (DG) and CA3 hippocampal subregions support pattern separation by inferring the nature of underlying representations from the observation of novelty signals. Here, we use ultra-high-resolution fMRI at 7 T and multivariate pattern analysis to provide compelling evidence that the DG subregion specifically sustains representations of similar scenes that are less overlapping than in other hippocampal (e.g., CA3) and medial temporal lobe regions (e.g., entorhinal cortex). Further, we provide evidence that novelty signals within the DG are stimulus specific rather than generic in nature. Our study, in providing a mechanistic link between novelty signals and the underlying representations, constitutes the first demonstration that the human DG performs pattern separation. SIGNIFICANCE STATEMENT A fundamental property of an episodic memory system is the ability to minimize interference between similar episodes. The dentate gyrus (DG) subregion of the hippocampus is widely viewed to realize this function through a computation referred to as pattern separation, which creates distinct nonoverlapping neural codes for individual events. Here, we leveraged 7 T fMRI to test the hypothesis that this region supports pattern separation. Our results demonstrate that the DG supports representations of similar scenes that are less overlapping than those in neighboring subregions. The current study therefore is the first to offer compelling evidence that the human DG supports pattern separation by obtaining critical empirical data at the representational level: the level where this computation is defined.

Cortical microinfarcts on 3T MRI: Clinical correlates in memory-clinic patients

This is the first study to assess cerebral microinfarcts (CMIs) on 3 tesla (3T) magnetic resonance imaging (MRI) in a memory clinic population.

Association between Subcortical Vascular Lesion Location and Cognition: A Voxel-Based and Tract-Based Lesion-Symptom Mapping Study. The SMART-MR Study

Introduction Lacunar lesions (LLs) and white matter lesions (WMLs) affect cognition. We assessed whether lesions located in specific white matter tracts were associated with cognitive performance taking into account total lesion burden. Methods Within the Second Manifestations of ARTerial disease Magnetic Resonance (SMART-MR) study, cross-sectional analyses were performed on 516 patients with manifest arterial disease. We applied an assumption-free voxel-based lesion-symptom mapping approach to investigate the relation between LL and WML locations on 1.5 Tesla brain MRI and compound scores of executive functioning, memory and processing speed. Secondly, a multivariable linear regression model was used to relate the regional volume of LLs and WMLs within specific white matter tracts to cognitive functioning. Results Voxel-based lesion-symptom mapping identified several clusters of voxels with a significant correlation between WMLs and executive functioning, mostly located within the superior longitudinal fasciculus and anterior thalamic radiation. In the multivariable linear regression model, a statistically significant association was found between regional LL volume within the superior longitudinal fasciculus and anterior thalamic radiation and executive functioning after adjustment for total LL and WML burden. Conclusion These findings identify the superior longitudinal fasciculus and anterior thalamic radiation as key anatomical structures in executive functioning and emphasize the role of strategically located vascular lesions in vascular cognitive impairment.

Efficient detection of cerebral microbleeds on 7.0 T MR images using the radial symmetry transform.

Cerebral microbleeds (CMBs) are commonly detected on MRI and have recently received an increased interest, because they are associated with vascular disease and dementia. Identification and rating of CMBs on MRI images may be facilitated by semi-automatic detection, particularly on high-resolution images acquired at high field strength. For these images, visual rating is time-consuming and has limited reproducibility. We present the radial symmetry transform (RST) as an efficient method for semi-automated CMB detection on 7.0 T MR images, with a high sensitivity and a low number of false positives that have to be censored manually. The RST was computed on both echoes of a dual-echo T2*-weighted gradient echo 7.0 T MR sequence in 18 participants from the Second Manifestations of ARTerial disease (SMART) study. Potential CMBs were identified by combining the output of the transform on both echoes. Each potential CMB identified through the RST was visually checked by two raters to identify probable CMBs. The scoring time needed to manually reject false positives was recorded. The sensitivity of 71.2% is higher than that of individual human raters on 7.0 T scans and the required human rater time is reduced from 30 to 2 minutes per scan on average. The RST outperforms published semi-automated methods in terms of either a higher sensitivity or less false positives, and requires much less human rater time.

Cerebral Microvascular Lesions on High-Resolution 7-Tesla MRI in Patients With Type 2 Diabetes

Cerebral small vessel disease, including microvascular lesions, is considered to play an important role in the development of type 2 diabetes mellitus (T2DM)-associated cognitive deficits. With ultra-high field MRI, microvascular lesions (e.g., microinfarcts and microbleeds) can now be visualized in vivo. For the current study, 48 nondemented older individuals with T2DM (mean age 70.3 ± 4.1 years) and 49 age-, sex-, and education-matched control subjects underwent a 7-Tesla brain MRI scan and a detailed cognitive assessment. The occurrence of cortical microinfarcts and cerebral microbleeds was assessed on fluid-attenuated inversion recovery and T1-weighted and T2*-weighted images, respectively, compared between the groups, and related to cognitive performance. Microinfarcts were found in 38% of control subjects and 48% of patients with T2DM. Microbleeds were present in 41% of control subjects and 33% of patients (all P > 0.05). The presence and number of microinfarcts or microbleeds were unrelated to cognitive performance. This study showed that microvascular brain lesions on ultra-high field MRI are not significantly more common in well-controlled patients with T2DM than in control subjects.

Visualization of perivascular spaces and perforating arteries with 7 T magnetic resonance imaging.

ObjectivesThe objectives of this study were to explore the possibilities of 7 T brain magnetic resonance imaging to visualize perivascular spaces (PVS) and to depict their related blood vessels. Materials and MethodsFive subjects aged 19 to 27 years and 5 subjects aged 51 to 72 years were scanned. High-resolution 3-dimensional T1-, T2-, as well as T2*-weighted sequences and time-of-flight angiography were used for the visualization of PVS, veins, and perforating arteries. Three extra subjects were scanned with a 2-dimensional time-of-flight sequence tailored to visualize small arteries and veins in the semioval center. The anatomy of PVS and their spatial relation with blood vessels were examined. The number and size of PVS in the semioval center were compared between the 2 groups. ResultsIn the basal ganglia, PVS were connected to the basal cisterns. Prominent dilations were observed in these PVS around the lower end of the putamen. From here, they ran upward and frequently showed caliber changes along their track. In the semioval center, smoothly shaped PVS started a few millimeters below the cortex, converged and tapered toward the ventricles, and ended 1 to 2 cm before the ventricle wall. Perivascular spaces correlated spatially with lenticulostriate arteries and with perforating arteries in the semioval center, but not with veins. The mean (SD) number of PVS was larger in the older subjects (55 [14]) than in the younger subjects (22 [11]), (P = 0.004). No difference in PVS diameter was observed. ConclusionsSeven-tesla magnetic resonance imaging offers detailed 3-dimensional visualization of PVS, their morphological features, and their related perforating arteries. This may offer new opportunities to study the role of PVS in ageing and cerebral small vessel disease.

Assessment of blood flow velocity and pulsatility in cerebral perforating arteries with 7‐T quantitative flow MRI

Thus far, blood flow velocity measurements with MRI have only been feasible in large cerebral blood vessels. High‐field‐strength MRI may now permit velocity measurements in much smaller arteries. The aim of this proof of principle study was to measure the blood flow velocity and pulsatility of cerebral perforating arteries with 7‐T MRI. A two‐dimensional (2D), single‐slice quantitative flow (Qflow) sequence was used to measure blood flow velocities during the cardiac cycle in perforating arteries in the basal ganglia (BG) and semioval centre (CSO), from which a mean normalised pulsatility index (PI) per region was calculated (n = 6 human subjects, aged 23–29 years). The precision of the measurements was determined by repeated imaging and performance of a Bland–Altman analysis, and confounding effects of partial volume and noise on the measurements were simulated. The median number of arteries included was 14 in CSO and 19 in BG. In CSO, the average velocity per volunteer was in the range 0.5–1.0 cm/s and PI was 0.24–0.39. In BG, the average velocity was in the range 3.9–5.1 cm/s and PI was 0.51–0.62. Between repeated scans, the precision of the average, maximum and minimum velocity per vessel decreased with the size of the arteries, and was relatively low in CSO and BG compared with the M1 segment of the middle cerebral artery. The precision of PI per region was comparable with that of M1. The simulations proved that velocities can be measured in vessels with a diameter of more than 80 µm, but are underestimated as a result of partial volume effects, whilst pulsatility is overestimated. Blood flow velocity and pulsatility in cerebral perforating arteries have been measured directly in vivo for the first time, with moderate to good precision. This may be an interesting metric for the study of haemodynamic changes in aging and cerebral small vessel disease.