Neuropathologic and Cognitive Correlates of Enlarged Perivascular Spaces in a Community-Based Cohort of Older Adults.

BACKGROUND AND PURPOSE: Enlarged perivascular spaces (EPVS) have been associated with aging, increased stroke risk, decreased cognitive function, and vascular dementia. However, the relationship of EPVS with age-related neuropathologies is not well understood. Therefore, the purpose of this study was to assess the neuropathologic correlates of EPVS in a large community-based cohort of older adults. The cognitive correlates of EPVS over and beyond those of other pathologies were also assessed. METHODS: This study included 654 older deceased and autopsied participants of 3 longitudinal community-based studies of aging that had available data on cognition, ex vivo brain magnetic resonance imaging, and detailed neuropathologic examination. EPVS seen on ex vivo magnetic resonance imaging were histologically validated. Experienced observers rated EPVS burden in ex vivo magnetic resonance imaging using a semiquantitative 4-level scale. Elastic-net regularized ordinal logistic regression was used to investigate associations of EPVS burden with age-related neuropathologies. Mixed-effects models of cognition controlling for neuropathologies, demographics, and clinical factors, were used to determine whether EPVS burden has additional contributions to cognitive decline. RESULTS: EPVS burden in the whole group was associated with gross infarcts (odds ratio=1.67, P=0.0017) and diabetes mellitus (odds ratio=1.73, P=0.004). When considering only nondemented participants (with mild or no cognitive impairment), EPVS burden was associated with gross infarcts (odds ratio=1.74, P=0.016) and microscopic infarcts (odds ratio=1.79, P=0.013). EPVS burden was associated with faster decline in visuospatial abilities (estimate=-0.009, P=0.028), in the whole group, as well as lower levels of semantic memory (estimate=-0.13, P=0.048) and visuospatial abilities (estimate=-0.11, P=0.016) at the time of death. CONCLUSIONS: EPVS and infarcts may share similar neurobiological pathways regardless of dementia status. EPVS burden is linked to diabetes mellitus independently of neuropathologies, extending recent findings in animal studies implicating diabetes mellitus in impairment of the glymphatic system. Finally, EPVS burden may reflect additional brain tissue injury that may contribute to cognitive decline, not captured with traditional neuropathologic measures.

Rapid PROPELLER-MRI: a combination of iterative reconstruction and under-sampling.

PURPOSE: To develop a technique that is able to reduce acquisition time and remove uneven blurring in reconstructed image for PROPELLER MRI. By using under-sampling and iterative reconstruction, this proposed technique will be less sensitive to subject motion. MATERIALS AND METHODS: Numerical simulations, as well as experiments on a phantom and healthy human subjects were performed to demonstrate advantages of a combination of under-sampled acquisition and iterative reconstruction. Method of motion correction was modified to increase accuracy of motion correction for the under-sampled PROPELLER acquisition. RESULTS: It was demonstrated that the proposed approach achieved substantial acceleration of PROPELLER acquisition while maintaining its motion correction advantage. CONCLUSION: An effective method for reducing imaging time in PROPELLER was introduced in this study, which minimizes typical under-sampling artifacts without uneven spatial resolution and maintains the ability of motion correction.

Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is associated with lower R2 relaxation rate: an ex-vivo MRI and pathology investigation.

Limbic predominant age-related transactive response DNA binding protein 43 (TDP-43) encephalopathy neuropathological change (LATE-NC) is common in persons older than 80 years of age and is associated with cognitive decline and increased likelihood of dementia. The MRI signature of LATE-NC has not been fully determined. In this study, the association of LATE-NC with the transverse relaxation rate, R2, was investigated in a large number of community-based older adults. Cerebral hemispheres from 738 participants of the Rush Memory and Aging Project, Religious Orders Study, and Minority Aging Research Study, were imaged ex-vivo with multi-echo spin-echo MRI and underwent detailed neuropathologic examination. Voxel-wise analysis revealed a novel spatial pattern of lower R2 for higher LATE-NC stage, controlling for other neuropathologies and demographics. This pattern was consistent with the distribution of LATE-NC in gray matter, and also involved white matter providing temporo-temporal, fronto-temporal, and temporo-basal ganglia connectivity. Furthermore, analysis at different LATE-NC stages showed that R2 imaging may capture the general progression of LATE-NC, but only when TDP-43 inclusions extend beyond the amygdala.

Quantitative magnetization transfer imaging in human brain at 3 T via selective inversion recovery.

Quantitative magnetization transfer imaging yields indices describing the interactions between free water protons and immobile, macromolecular protons-including the macromolecular to free pool size ratio (PSR) and the rate of magnetization transfer between pools k(mf) . This study describes the first implementation of the selective inversion recovery quantitative magnetization transfer method on a clinical 3.0-T scanner in human brain in vivo. Selective inversion recovery data were acquired at 16 different inversion times in nine healthy subjects and two patients with relapsing remitting multiple sclerosis. Data were collected using a fast spin-echo readout and reduced repetition time, resulting in an acquisition time of 4 min for a single slice. In healthy subjects, excellent intersubject and intrasubject reproducibilities (assessed via repeated measures) were demonstrated. Furthermore, PSR values in white (mean ± SD = 11.4 ± 1.2%) and gray matter (7.5 ± 0.7%) were consistent with previously reported values, while k(mf) values were approximately 2-fold slower in both white (11 ± 2 s(-1) ) and gray matter (15 ± 6 s(-1) ). In relapsing remitting multiple sclerosis patients, quantitative magnetization transfer indices were sensitive to pathological changes in lesions and in normal appearing white matter.

ARTS: A novel In-vivo classifier of arteriolosclerosis for the older adult brain.

Brain arteriolosclerosis, one of the main pathologies of cerebral small vessel disease, is common in older adults and has been linked to lower cognitive and motor function and higher odds of dementia. In spite of its frequency and associated morbidity, arteriolosclerosis can only be diagnosed at autopsy. Therefore, the purpose of this work was to develop an in-vivo classifier of arteriolosclerosis based on brain MRI. First, an ex-vivo classifier of arteriolosclerosis was developed based on features related to white matter hyperintensities, diffusion anisotropy and demographics by applying machine learning to ex-vivo MRI and pathology data from 119 participants of the Rush Memory and Aging Project (MAP) and Religious Orders Study (ROS), two longitudinal cohort studies of aging that recruit non-demented older adults. The ex-vivo classifier showed good performance in predicting the presence of arteriolosclerosis, with an average area under the receiver operating characteristic curve AUC = 0.78. The ex-vivo classifier was then translated to in-vivo based on available in-vivo and ex-vivo MRI data on the same participants. The in-vivo classifier was named ARTS (short for ARTerioloSclerosis), is fully automated, and provides a score linked to the likelihood a person suffers from arteriolosclerosis. The performance of ARTS in predicting the presence of arteriolosclerosis in-vivo was tested in a separate, 91% dementia-free group of 79 MAP/ROS participants and exhibited an AUC = 0.79 in persons with antemortem intervals shorter than 2.4 years. This level of performance in mostly non-demented older adults is notable considering that arteriolosclerosis can only be diagnosed at autopsy. The scan-rescan reproducibility of the ARTS score was excellent, with an intraclass correlation of 0.99, suggesting that application of ARTS in longitudinal studies may show high sensitivity in detecting small changes. Finally, higher ARTS scores in non-demented older adults were associated with greater decline in cognition two years after baseline MRI, especially in perceptual speed which has been linked to arteriolosclerosis and small vessel disease. This finding was shown in a separate group of 369 non-demented MAP/ROS participants and was validated in 72 non-demented Black participants of the Minority Aging Research Study (MARS) and also in 244 non-demented participants of the Alzheimer's Disease Neuroimaging Initiative 2 and 3. The results of this work suggest that ARTS may have broad implications in the advancement of diagnosis, prevention and treatment of arteriolosclerosis. ARTS is publicly available at https://www.nitrc.org/projects/arts/.

Iterative image reconstruction for PROPELLER-MRI using the nonuniform fast fourier transform.

PURPOSE: To investigate an iterative image reconstruction algorithm using the nonuniform fast Fourier transform (NUFFT) for PROPELLER (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction) MRI. MATERIALS AND METHODS: Numerical simulations, as well as experiments on a phantom and a healthy human subject were used to evaluate the performance of the iterative image reconstruction algorithm for PROPELLER, and compare it with that of conventional gridding. The trade-off between spatial resolution, signal to noise ratio, and image artifacts, was investigated for different values of the regularization parameter. The performance of the iterative image reconstruction algorithm in the presence of motion was also evaluated. RESULTS: It was demonstrated that, for a certain range of values of the regularization parameter, iterative reconstruction produced images with significantly increased signal to noise ratio, reduced artifacts, for similar spatial resolution, compared with gridding. Furthermore, the ability to reduce the effects of motion in PROPELLER-MRI was maintained when using the iterative reconstruction approach. CONCLUSION: An iterative image reconstruction technique based on the NUFFT was investigated for PROPELLER MRI. For a certain range of values of the regularization parameter, the new reconstruction technique may provide PROPELLER images with improved image quality compared with conventional gridding.

Motion correction in periodically-rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) and turboprop MRI.

Periodically-rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) and Turboprop MRI are characterized by greatly reduced sensitivity to motion, compared to their predecessors, fast spin-echo (FSE) and gradient and spin-echo (GRASE), respectively. This is due to the inherent self-navigation and motion correction of PROPELLER-based techniques. However, it is unknown how various acquisition parameters that determine k-space sampling affect the accuracy of motion correction in PROPELLER and Turboprop MRI. The goal of this work was to evaluate the accuracy of motion correction in both techniques, to identify an optimal rotation correction approach, and determine acquisition strategies for optimal motion correction. It was demonstrated that blades with multiple lines allow more accurate estimation of motion than blades with fewer lines. Also, it was shown that Turboprop MRI is less sensitive to motion than PROPELLER. Furthermore, it was demonstrated that the number of blades does not significantly affect motion correction. Finally, clinically appropriate acquisition strategies that optimize motion correction are discussed for PROPELLER and Turboprop MRI.

Ex-vivo quantitative susceptibility mapping of human brain hemispheres.

Ex-vivo brain quantitative susceptibility mapping (QSM) allows investigation of brain characteristics at essentially the same point in time as histopathologic examination, and therefore has the potential to become an important tool for determining the role of QSM as a diagnostic and monitoring tool of age-related neuropathologies. In order to be able to translate the ex-vivo QSM findings to in-vivo, it is crucial to understand the effects of death and chemical fixation on brain magnetic susceptibility measurements collected ex-vivo. Thus, the objective of this work was twofold: a) to assess the behavior of magnetic susceptibility in both gray and white matter of human brain hemispheres as a function of time postmortem, and b) to establish the relationship between in-vivo and ex-vivo gray matter susceptibility measurements on the same hemispheres. Five brain hemispheres from community-dwelling older adults were imaged ex-vivo with QSM on a weekly basis for six weeks postmortem, and the longitudinal behavior of ex-vivo magnetic susceptibility in both gray and white matter was assessed. The relationship between in-vivo and ex-vivo gray matter susceptibility measurements was investigated using QSM data from eleven older adults imaged both antemortem and postmortem. No systematic change in ex-vivo magnetic susceptibility of gray or white matter was observed over time postmortem. Additionally, it was demonstrated that, gray matter magnetic susceptibility measured ex-vivo may be well modeled as a linear function of susceptibility measured in-vivo. In conclusion, magnetic susceptibility in gray and white matter measured ex-vivo with QSM does not systematically change in the first six weeks after death. This information is important for future cross-sectional ex-vivo QSM studies of hemispheres imaged at different postmortem intervals. Furthermore, the linear relationship between in-vivo and ex-vivo gray matter magnetic susceptibility suggests that ex-vivo QSM captures information linked to antemortem gray matter magnetic susceptibility, which is important for translation of ex-vivo QSM findings to in-vivo.

Contribution of cardiac-induced brain pulsation to the noise of the diffusion tensor in Turboprop diffusion tensor imaging (DTI).

PURPOSE: To assess the effects of cardiac-induced brain pulsation on the noise of the diffusion tensor in Turboprop (a form of periodically rotated overlapping parallel lines with enhanced reconstruction [PROPELLER] imaging) diffusion tensor imaging (DTI). MATERIALS AND METHODS: A total of six healthy human subjects were imaged with cardiac-gated as well as nongated Turboprop DTI. Gated and nongated Turboprop DTI datasets were also simulated using actual data acquired exclusively during the diastolic or systolic period of the cardiac cycle. The total variance of the diffusion tensor (TVDT) was measured and compared between acquisitions. RESULTS: The TVDT near the ventricles was significantly reduced in cardiac-gated compared to nongated Turboprop DTI acquisitions. Furthermore, the effects of brain pulsation were reduced, but not eliminated, when increasing the amount of data collected. Finally, data corrupted by cardiac-induced pulsation were not consistently detected by the step of the conventional Turboprop reconstruction algorithm that evaluates the quality of data in different blades. Thus, the inherent quality weighting of the conventional Turboprop reconstruction algorithm was unable to compensate for the increased noise in the diffusion tensor due to brain pulsation. CONCLUSION: Cardiac-induced brain pulsation increases the TVDT in Turboprop DTI. Use of cardiac gating to limit data acquisition to the diastolic period of the cardiac cycle reduces the TVDT at the expense of imaging time.

k-space undersampling in PROPELLER imaging.

PROPELLER MRI (periodically rotated overlapping parallel lines with enhanced reconstruction) provides images with significantly fewer B(0)-related artifacts than echo-planar imaging (EPI), as well as reduced sensitivity to motion compared to conventional multiple-shot fast spin-echo (FSE). However, the minimum imaging time in PROPELLER is markedly longer than in EPI and 50% longer than in conventional multiple-shot FSE. Often in MRI, imaging time is reduced by undersampling k-space. In the present study, the effects of undersampling on PROPELLER images were evaluated using simulated and in vivo data sets. Undersampling using PROPELLER patterns with reduced number of samples per line, number of lines per blade, or number of blades per acquisition, while maintaining the same k-space field of view (FOV(k)) and uniform sampling at the edges of FOV(k), reduced imaging time but led to severe image artifacts. In contrast, undersampling by means of removing whole blades from a PROPELLER sampling pattern that sufficiently samples k-space produced only minimal image artifacts, mainly manifested as blurring in directions parallel to the blades removed, even when reducing imaging time by as much as 50%. Finally, undersampling using asymmetric blades and taking advantage of Hermitian symmetries to fill-in the missing data significantly reduced imaging time without causing image artifacts.