Although cerebrovascular factors are the second leading cause of cognitive impairment and dementia in elderly, the precise spatial and temporal trajectories of vascular decline in aging have not been fully characterized. With an advanced cerebrovascular reactivity (CVR) MRI technique that specifically informs vascular stiffness and dilatory ability of cerebral vessels, we present four-year longitudinal CVR data measured in 116 healthy individuals (20-88 years of age). Our data revealed a spatial heterogeneity in vascular decline in aging (p = 0.003), in that temporal lobe showed the fastest rate of longitudinal CVR decline, followed by parietal and frontal lobes. The rate of CVR decline was also age-dependent. Middle age, not older age, manifested the fastest rate of longitudinal CVR decline (p < 0.05). Longitudinal changes in CVR were associated with changes in processing speed (p = 0.031) and episodic memory (p = 0.022), but not with working memory or reasoning. The rate of longitudinal CVR change was not different between hypertensive and normotensive participants. However, cross-sectionally, individuals with hypertension revealed in a lower CVR compared to normotensive participants (p = 0.016). These findings help elucidate age-related decline in brain hemodynamics and support CVR as a non-invasive biomarker in evaluating cerebrovascular conditions in elderly individuals.

Resting-state brain activity has been investigated extensively using BOLD contrast. However, BOLD signal represents the combined effects of multiple physiological processes and its spatial localization is less accurate than that of cerebral blood flow and volume (CBF and CBF, respectively). In this study, we demonstrate that resting-state brain activity can be reliably detected by spontaneous fluctuations of CBV-weighted signal using whole-brain gradient and spin echo (GRASE) based vascular space occupancy (VASO) imaging. Specifically, using independent component analysis, intrinsic brain networks, including default mode, salience, executive control, visual, auditory, and sensorimotor networks were revealed robustly by the VASO technique. We further demonstrate that task-evoked VASO signal aligned well with expected gray matter areas, while blood-oxygenation level dependent (BOLD) signal extended outside of these areas probably due to their different spatial specificity. The improved spatial localization of VASO is consistent with previous studies using animal models. Moreover, we showed that the 3D-GRASE VASO images had reduced susceptibility-induced signal voiding, compared to the BOLD technique. This is attributed to the fact that VASO does not require T2* weighting, thus the acquisition can use a shorter TE and can employ spin-echo scheme. Consequently VASO-based functional connectivity signals were well preserved in brain regions that tend to suffer from signal loss and geometric distortion in BOLD, such as orbital prefrontal cortex. Our study suggests that 3D-GRASE VASO imaging, with its improved spatial specificity and less sensitivity to susceptibility artifacts, may have advantages in resting-state fMRI studies.

Background

With the disappointing outcomes of clinical trials on patients with Alzheimer's disease or mild cognitive impairment (MCI), there is increasing attention to understanding cognitive decline in normal elderly individuals, with the goal of identifying subjects who are most susceptible to imminent cognitive impairment.

Purpose/hypothesis

To evaluate the potential of cerebral blood flow (CBF) as a biomarker by investigating the relationship between CBF at baseline and cognition at follow-up.

Study type

Prospective longitudinal study with a 4-year time interval.

Population

309 healthy subjects aged 20-89 years old.

Field strength/sequence

3T pseudo-continuous-arterial-spin-labeling MRI.

Assessment

CBF at baseline and cognitive assessment at both baseline and follow-up.

Statistical tests

Linear regression analyses with age, systolic blood pressure, physical activity, and baseline cognition as covariates.

Results

Linear regression analyses revealed that whole-brain CBF at baseline was predictive of general fluid cognition at follow-up. This effect was observed in the older group (age ≥54 years, β = 0.221, P = 0.004), but not in younger or entire sample (β = 0.018, P = 0.867 and β = 0.089, P = 0.098, respectively). Among major brain lobes, frontal CBF had the highest sensitivity in predicting future cognition, with a significant effect observed for fluid cognition (β = 0.244 P = 0.001), episodic memory (β = 0.294, P = 0.001), and reasoning (β = 0.186, P = 0.027). These associations remained significant after accounting for baseline cognition. Voxelwise analysis revealed that medial frontal cortex and anterior cingulate cortex, part of the default mode network (DMN), are among the most important regions in predicting fluid cognition.

Data conclusion

In a healthy aging cohort, CBF can predict general cognitive ability as well as specific domains of cognitive function.

Level of evidence

1 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2018;48:449-458.

Insidious declines in normal aging are well-established. Emerging evidence suggests that non-pharmacological interventions, specifically cognitive and physical training, may counter diminishing age-related cognitive and brain functions. This randomized trial compared effects of two training protocols: cognitive training (CT) vs. physical training (PT) on cognition and brain function in adults 56-75 years. Sedentary participants (N = 36) were randomized to either CT or PT group for 3 h/week over 12 weeks. They were assessed at baseline-, mid-, and post-training using neurocognitive, MRI, and physiological measures. The CT group improved on executive function whereas PT group's memory was enhanced. Uniquely deploying cerebral blood flow (CBF) and cerebral vascular reactivity (CVR) MRI, the CT cohort showed increased CBF within the prefrontal and middle/posterior cingulate cortex (PCC) without change to CVR compared to PT group. Improvements in complex abstraction were positively associated with increased resting CBF in dorsal anterior cingulate cortex (dACC). Exercisers with higher CBF in hippocampi bilaterally showed better immediate memory. The preliminary evidence indicates that increased cognitive and physical activity improves brain health in distinct ways. Reasoning training enhanced frontal networks shown to be integral to top-down cognitive control and brain resilience. Evidence of increased resting CBF without changes to CVR implicates increased neural health rather than improved vascular response. Exercise did not improve cerebrovascular response, although CBF increased in hippocampi of those with memory gains. Distinct benefits incentivize testing effectiveness of combined protocols to strengthen brain health.

Identifying biosignatures to assess the probability of response to an antidepressant for patients with major depressive disorder (MDD) is critically needed. Functional connectivity MRI (fcMRI) offers the promise to provide such a measure. Previous work with fcMRI demonstrated that the correlation in signal from one region to another is a measure of functional connectivity. In this pilot work, a baseline non-task fcMRI was acquired in 14 adults with MDD who were free of all medications. Participants were then treated for 8 weeks with an antidepressant and then clinically re-evaluated. Probabilistic anatomic regions of interest (ROI) were defined for 16 brain regions (eight for each hemisphere) previously identified as being important in mood disorders. These ROIs were used to determine mean time courses for each individual's baseline non-task fcMRI. The correlations in time courses between 16 brain regions were calculated. These calculated correlations were considered to signify measures of functional connectivity. The degree of connectivity for each participant was correlated with treatment outcome. Among 13 participants with 8 weeks follow-up data, connectivity measures in several regions, especially the subcallosal cortex, were highly correlated with treatment outcome. These connectivity measures could provide a means to evaluate how likely a patient is to respond to an antidepressant treatment. Further work using larger samples is required to confirm these findings and to assess if measures of functional connectivity can be used to predict differential outcomes between antidepressant treatments.

Insidious declines in normal aging are well-established. Emerging evidence suggests that non-pharmacological interventions, specifically cognitive and physical training, may counter diminishing age-related cognitive and brain functions. This randomized trial compared effects of two training protocols: cognitive training (CT) vs. physical training (PT) on cognition and brain function in adults 56-75 years. Sedentary participants (N = 36) were randomized to either CT or PT group for 3 h/week over 12 weeks. They were assessed at baseline-, mid-, and post-training using neurocognitive, MRI, and physiological measures. The CT group improved on executive function whereas PT group's memory was enhanced. Uniquely deploying cerebral blood flow (CBF) and cerebral vascular reactivity (CVR) MRI, the CT cohort showed increased CBF within the prefrontal and middle/posterior cingulate cortex (PCC) without change to CVR compared to PT group. Improvements in complex abstraction were positively associated with increased resting CBF in dorsal anterior cingulate cortex (dACC). Exercisers with higher CBF in hippocampi bilaterally showed better immediate memory. The preliminary evidence indicates that increased cognitive and physical activity improves brain health in distinct ways. Reasoning training enhanced frontal networks shown to be integral to top-down cognitive control and brain resilience. Evidence of increased resting CBF without changes to CVR implicates increased neural health rather than improved vascular response. Exercise did not improve cerebrovascular response, although CBF increased in hippocampi of those with memory gains. Distinct benefits incentivize testing effectiveness of combined protocols to strengthen brain health.

The relationship between functional brain activity and gene expression has not been fully explored in the human brain. Here, we identify significant correlations between gene expression in the brain and functional activity by comparing fractional amplitude of low-frequency fluctuations (fALFF) from two independent human fMRI resting-state datasets to regional cortical gene expression from a newly generated RNA-seq dataset and two additional gene expression datasets to obtain robust and reproducible correlations. We find significantly more genes correlated with fALFF than expected by chance and identify specific genes correlated with the imaging signals in multiple expression datasets in the default mode network. Together, these data support a population-level relationship between regional steady-state brain gene expression and resting-state brain activity.

This review provides a summary statement of recommended implementations of arterial spin labeling (ASL) for clinical applications. It is a consensus of the ISMRM Perfusion Study Group and the European ASL in Dementia consortium, both of whom met to reach this consensus in October 2012 in Amsterdam. Although ASL continues to undergo rapid technical development, we believe that current ASL methods are robust and ready to provide useful clinical information, and that a consensus statement on recommended implementations will help the clinical community to adopt a standardized approach. In this review, we describe the major considerations and trade-offs in implementing an ASL protocol and provide specific recommendations for a standard approach. Our conclusion is that as an optimal default implementation, we recommend pseudo-continuous labeling, background suppression, a segmented three-dimensional readout without vascular crushing gradients, and calculation and presentation of both label/control difference images and cerebral blood flow in absolute units using a simplified model.

This review provides a summary statement of recommended implementations of arterial spin labeling (ASL) for clinical applications. It is a consensus of the ISMRM Perfusion Study Group and the European ASL in Dementia consortium, both of whom met to reach this consensus in October 2012 in Amsterdam. Although ASL continues to undergo rapid technical development, we believe that current ASL methods are robust and ready to provide useful clinical information, and that a consensus statement on recommended implementations will help the clinical community to adopt a standardized approach. In this review, we describe the major considerations and trade-offs in implementing an ASL protocol and provide specific recommendations for a standard approach. Our conclusion is that as an optimal default implementation, we recommend pseudo-continuous labeling, background suppression, a segmented three-dimensional readout without vascular crushing gradients, and calculation and presentation of both label/control difference images and cerebral blood flow in absolute units using a simplified model. Magn Reson Med 73:102-116, 2015. © 2014 Wiley Periodicals, Inc.

Pretreatment CT Perfusion (CTP) parameter rCBV < 42% lesion volume has recently been shown to predict 90-day mRS. In this study, we aim to assess the relationship between rCBV < 42% and a radiographic follow-up infarct volume delineated on FLAIR images. In this retrospective evaluation of our prospectively collected database, we included acute stroke patients triaged by multimodal CT imaging, including CT angiography and perfusion imaging, with confirmed anterior circulation large vessel occlusion between 9 January 2017 and 10 January 2023. Follow-up FLAIR imaging was used to determine the final infarct volume. Student t, Mann-Whitney-U, and Chi-Square tests were used to assess differences. Spearmans rank correlation and linear regression analysis were used to assess associations between rCBV < 42% and follow-up infarct volume on FLAIR. In total, 158 patients (median age: 68 years, 52.5% female) met our inclusion criteria. rCBV < 42% (ρ = 0.56, p < 0.001) significantly correlated with follow-up-FLAIR infarct volume. On multivariable linear regression analysis, rCBV < 42% lesion volume (beta = 0.60, p < 0.001), ASPECTS (beta = -0.214, p < 0.01), mTICI (beta = -0.277, p < 0.001), and diabetes (beta = 0.16, p < 0.05) were independently associated with follow-up infarct volume. The rCBV < 42% lesion volume is independently associated with FLAIR follow-up infarct volume.