Age-related differences in cerebral blood flow and cortical thickness with an application to age prediction.

Cerebral cortex thinning and cerebral blood flow (CBF) reduction are typically observed during normal healthy aging. However, imaging-based age prediction models have primarily used morphological features of the brain. Complementary physiological CBF information might result in an improvement in age estimation. In this study, T1-weighted structural magnetic resonance imaging and arterial spin labeling CBF images were acquired in 146 healthy participants across the adult life span. Sixty-eight cerebral cortex regions were segmented, and the cortical thickness and mean CBF were computed for each region. Linear regression with age was computed for each region and data type, and laterality and correlation matrices were computed. Sixteen predictive models were trained with the cortical thickness and CBF data alone as well as a combination of both data types. The age explained more variance in the cortical thickness data (average R2 of 0.21) than in the CBF data (average R2 of 0.09). All 16 models performed significantly better when combining both measurement types and using feature selection, and thus, we conclude that the inclusion of CBF data marginally improves age estimation.

Cerebrovascular reactivity in cerebral amyloid angiopathy, Alzheimer disease, and mild cognitive impairment.

OBJECTIVE: To assess cerebrovascular reactivity in response to a visual task in participants with cerebral amyloid angiopathy (CAA), Alzheimer disease (AD), and mild cognitive impairment (MCI) using fMRI. METHODS: This prospective cohort study included 40 patients with CAA, 22 with AD, 27 with MCI, and 25 healthy controls. Each participant underwent a visual fMRI task using a contrast-reversing checkerboard stimulus. Visual evoked potentials (VEPs) were used to compare visual cortex neuronal activity in 83 participants. General linear models using least-squares means, adjusted for multiple comparisons with the Tukey test, were used to estimate mean blood oxygen level-dependent (BOLD) signal change during the task and VEP differences between groups. RESULTS: After adjustment for age and hypertension, estimated mean BOLD response amplitude was as follows: CAA 1.88% (95% confidence interval [CI] 1.60%-2.15%), AD 2.26% (1.91%-2.61%), MCI 2.15% (1.84%-2.46%), and control 2.65% (2.29%-3.00%). Only patients with CAA differed from controls (p = 0.01). In the subset with VEPs, group was not associated with prolonged latencies or lower amplitudes. Lower BOLD amplitude response was associated with higher white matter hyperintensity (WMH) volumes in CAA (for each 0.1% lower BOLD response amplitude, the WMH volume was 9.2% higher, 95% CI 6.0%-12.4%) but not other groups (p = 0.002 for interaction) when controlling for age and hypertension. CONCLUSIONS: Mean visual BOLD response amplitude was lowest in participants with CAA compared to controls, without differences in VEP latencies and amplitudes. This suggests that the impaired visual BOLD response is due to reduced vascular reactivity in CAA. In contrast to participants with CAA, the visual BOLD response amplitude did not differ between those with AD or MCI and controls.

Perfusion has no effect on the in vivo CEST effect from Cr (CrCEST) in skeletal muscle.

Creatine, a key component of muscle energy metabolism, exhibits a chemical exchange saturation transfer (CEST) effect between its amine group and bulk water, which has been exploited to spatially and temporally map creatine changes in skeletal muscle before and after exercise. In addition, exercise leads to an increase in muscle perfusion. In this work, we determined the effects of perfused blood on the CEST effects from creatine in skeletal muscle. Experiments were performed on healthy human subjects (n = 5) on a whole-body Siemens 7T magnetic resonance imaging (MRI) scanner with a 28-channel radiofrequency (RF) coil. Reactive hyperemia, induced by inflation and subsequent deflation of a pressure cuff secured around the thigh, was used to increase tissue perfusion whilst maintaining the levels of creatine kinase metabolites. CEST, arterial spin labeling (ASL) and 31 P MRS data were acquired at baseline and for 6 min after cuff deflation. Reactive hyperemia resulted in substantial increases in perfusion in human skeletal muscle of the lower leg as measured by the ASL mean percentage difference. However, no significant changes in CrCEST asymmetry (CrCESTasym ) or 31 P MRS-derived PCr levels of skeletal muscle were observed following cuff deflation. This work demonstrates that perfusion changes do not have a major confounding effect on CrCEST measurements.

An Actively Decoupled Dual Transceiver Coil System for Continuous ASL at 7 T.

7 T arterial spin labeling (ASL) faces major challenges including the increased specific absorption rate (SAR) and increased B0 and B1 inhomogeneity. This work describes the design and implementation of a dual-coil system that allows for continuous ASL (CASL) at 7 T. This system consisted of an actively detunable eight-channel transceiver head coil, and a three-channel transceiver labeling coil. Four experiments were performed in 5 healthy subjects: (i) to demonstrate that active detuning during ASL labeling reduces magnetization transfer; (ii) to measure the B1 profile at the labeling plane; (iii) to quantify B0 off-resonance at the labeling plane; and (iv) to collect in vivo CASL data. The magnetization transfer ratio in the head coil was reduced to 0.0 ± 0.2% by active detuning during labeling. The measured B1 profiles in all 5 subjects were sufficient to satisfy the flow-driven adiabatic inversion necessary for CASL, however the actual labeling efficiency was significantly impacted by B0 off-resonance at the labeling plane. The measured CASL percent signal change in gray matter (0.94% ± 0.10%) corresponds with the low labeling efficiency predicted by the B0 off-resonance. This work demonstrates progress in the technical implementation of 7 T CASL, and reinforces the need for improved B0 homogeneity at the labeling plane.

Comparison of non-invasive MRI measurements of cerebral blood flow in a large multisite cohort.

UNLABELLED: Arterial spin labeling and phase contrast magnetic resonance imaging provide independent non-invasive methods for measuring cerebral blood flow. We compared global cerebral blood flow measurements obtained using pseudo-continuous arterial spin labeling and phase contrast in 436 middle-aged subjects acquired at two sites in the NHLBI CARDIA multisite study. Cerebral blood flow measured by phase contrast (CBFPC: 55.76 ± 12.05 ml/100 g/min) was systematically higher (p < 0.001) and more variable than cerebral blood flow measured by pseudo-continuous arterial spin labeling (CBFPCASL: 47.70 ± 9.75). The correlation between global cerebral blood flow values obtained from the two modalities was 0.59 (p < 0.001), explaining less than half of the observed variance in cerebral blood flow estimates. Well-established correlations of global cerebral blood flow with age and sex were similarly observed in both CBFPCASL and CBFPC CBFPC also demonstrated statistically significant site differences, whereas no such differences were observed in CBFPCASL No consistent velocity-dependent effects on pseudo-continuous arterial spin labeling were observed, suggesting that pseudo-continuous labeling efficiency does not vary substantially across typical adult carotid and vertebral velocities, as has previously been suggested. CONCLUSIONS: Although CBFPCASL and CBFPC values show substantial similarity across the entire cohort, these data do not support calibration of CBFPCASL using CBFPC in individual subjects. The wide-ranging cerebral blood flow values obtained by both methods suggest that cerebral blood flow values are highly variable in the general population.

Longitudinal decrease in blood oxygenation level dependent response in cerebral amyloid angiopathy.

Lower blood oxygenation level dependent (BOLD) signal changes in response to a visual stimulus in functional magnetic resonance imaging (fMRI) have been observed in cross-sectional studies of cerebral amyloid angiopathy (CAA), and are presumed to reflect impaired vascular reactivity. We used fMRI to detect a longitudinal change in BOLD responses to a visual stimulus in CAA, and to determine any correlations between these changes and other established biomarkers of CAA progression. Data were acquired from 22 patients diagnosed with probable CAA (using the Boston Criteria) and 16 healthy controls at baseline and one year. BOLD data were generated from the 200 most active voxels of the primary visual cortex during the fMRI visual stimulus (passively viewing an alternating checkerboard pattern). In general, BOLD amplitudes were lower at one year compared to baseline in patients with CAA (p = 0.01) but were unchanged in controls (p = 0.18). The longitudinal difference in BOLD amplitudes was significantly lower in CAA compared to controls (p < 0.001). White matter hyperintensity (WMH) volumes and number of cerebral microbleeds, both presumed to reflect CAA-mediated vascular injury, increased over time in CAA (p = 0.007 and p = 0.001, respectively). Longitudinal increases in WMH (rs = 0.04, p = 0.86) or cerebral microbleeds (rs = -0.18, p = 0.45) were not associated with the longitudinal decrease in BOLD amplitudes.

Improved susceptibility weighted imaging method using multi-echo acquisition.

PURPOSE: To introduce novel acquisition and postprocessing approaches for susceptibility weighted imaging (SWI) to remove background field inhomogeneity artifacts in both magnitude and phase data. METHODS: The proposed method acquires three echoes in a three-dimensional gradient echo (GRE) sequence, with a field compensation gradient (z-shim gradient) applied to the third echo. The artifacts in the magnitude data are compensated by signal estimation from all three echoes. The artifacts in phase signals are removed by modeling the background phase distortions using Gaussians. The method was applied in vivo and compared with conventional SWI. RESULTS: The method successfully compensates for background field inhomogeneity artifacts in magnitude and phase images, and demonstrated improved SWI images. In particular, vessels in frontal lobe, which were not observed in conventional SWI, were identified in the proposed method. CONCLUSION: The new method improves image quality in SWI by restoring signal in the frontal and temporal regions.

Accelerated passive MR catheter tracking into the carotid artery of canines.

BACKGROUND: Using magnetic resonance (MR) imaging for navigating catheters has several advantages when compared with the current "gold standard" modality of X-ray imaging. A significant drawback to interventional MR is inferior temporal and spatial resolutions, as high spatial resolution images cannot be collected and displayed at rates equal to X-ray imaging. In particular, passive MR catheter tracking experiments that use positive contrast mechanisms have poor temporal imaging rates and signal-to-noise ratio. As a result, with passive methods, it is often difficult to reconstruct motion artifact-free tracking images from areas with motion, such as the thoracic cavity. METHODS: In this study, several accelerated MR acquisition strategies, including parallel imaging and compressed sensing (CS), were evaluated to determine which method is most effective at improving the frame rate and passive detection of catheters in regions of physiological motion. Device navigation was performed both in vitro, through the aortic arch of an anthropomorphic chest phantom, and in vivo from the femoral artery, up the descending aorta into the supra-aortic branching vessels in canines. RESULTS AND DISCUSSION: The different parallel imaging methods produced images of low quality. CS with a two-fold acceleration was found to be the most effective method for generating tracking images, improving the image frame rate to 5.2 Hz, while maintaining a relatively high in-plane resolution. Using CS, motion artifact was decreased and the catheters were visualized with good conspicuity near the heart. CONCLUSIONS: The improvement in the imaging frame rate by image acceleration was sufficient to overcome motion artifacts and to better visualize catheters in the thoracic cavity with passive tracking. CS preformed best at tracking. Navigation with passive MR catheter tracking was demonstrated from the femoral artery to the carotid artery in canines.

Microvascular perfusion based on arterial spin labeled perfusion MRI as a measure of vascular risk in Alzheimer's disease.

There is growing recognition of an interaction between cerebrovascular disease and Alzheimer's disease, but the mechanisms of this interaction remain poorly understood. While macroscopic stroke can clearly produce cognitive deficits and accelerate Alzheimer's disease, the prevalence and implications of microvascular disease in Alzheimer's disease pathogenesis has been harder to define. At present, white matter (WM) lesions, primarily defined as hyperintensities seen on T2-weighted magnetic resonance imaging (MRI), provide the best biomarker of cerebrovascular disease at the microvascular level. However, T2 hyperintensities in WM can also be caused by other mechanisms such as inflammation. Arterial spin labeled (ASL) perfusion MRI provides a noninvasive approach for quantifying cerebral blood flow (CBF). We explored CBF measurements with ASL in AD patients, mild cognitive impairment patients, and an age-matched control group to determine if CBF in gray matter or WM could be correlated with WM lesions, or to stratify patients by microvascular disease severity. In a retrospective sample, we were able to obtain credible measures of WM CBF using ASL MRI and observed trends suggesting that WM CBF may provide a useful biomarker of microvascular disease. Future prospective studies in larger cohorts with optimized ASL MRI protocols will be needed to validate these observations.

Unenhanced MR angiography of the renal arteries with balanced steady-state free precession dixon method.

OBJECTIVE: The purpose of this study was to evaluate the feasibility of a novel technique for fat-water separation to image the renal arteries without using a contrast agent. CONCLUSION: Five healthy volunteers were imaged on a 3-T clinical MR scanner using the balanced steady-state free precession (SSFP) Dixon method. We were able to image the proximal renal arteries with high conspicuity within a 3-minute overall scanning time. The balanced-SSFP Dixon method shows potential for unenhanced MR angiography of the proximal renal arteries.

3D non-contrast-enhanced MR angiography with balanced steady-state free precession Dixon method.

Balanced steady-state free precession (bSSFP) is capable of producing ample fat-water separation. In the case of the bSSFP Dixon method, the phase between fat and water can be manipulated by setting repetition time (TR) to an odd-half-multiple of the cycle time and adjusting the center frequency to acquire fat-water in in-phase and opposed-phase images. Adding an image collected when fat and water are in-phase to an image in which fat and water are opposed-phase produces a water-only image. Of the water signals, arterial blood has the highest T(2)/T(1) contrast, making the arterial signal appear brighter than both venous blood and muscle in the final image. In this study, the bSSFP Dixon method was used to collect coronal water-only three-dimensional (3D) volumes at multiple anatomical stations in the legs of five healthy volunteers. The image quality was quantified by region-of-interest (ROI) analysis of signal intensities between arterial blood, venous blood, muscle, and fat. The images were also assessed for diagnostic quality by a trained radiologist. The bSSFP Dixon method was successful in producing non-contrast-enhanced (NCE) images of the blood vessels in the lower limbs. The work presented here is a proof-of-concept for the use of the bSSFP Dixon method for 3D peripheral angiography.

Magnetization evolution in balanced steady-state free precession with continuously moving table.

Diagnostic imaging of systemic disorders, such as peripheral vascular diseases, requires a field-of-view (FOV) larger than the local FOV available on clinical MR scanners. The continuously moving table (CMT) method acquires large FOV images in a single acquisition. Balanced steady-state free precession (bSSFP) is an attractive candidate for the CMT method due to its short repetition time and high signal-to-noise ratio. However, introducing table motion during data acquisition perturbs the magnetization evolution towards steady state. In this paper, a computer model was developed to simulate the bSSFP magnetization evolution in the presence of table motion. From these simulations, predictions were made about the maximum table velocities that would allow the magnetizations of specific tissues to evolve to the theoretical steady-state values. These predicted maximum table velocities were then successfully verified in vivo with bSSFP CMT acquisitions. For an imaging FOV