Whole-Cerebrum distortion-free three-dimensional pseudo-continuous arterial spin labeling at 7T.

Fulfilling potentials of ultrahigh field for pseudo-Continuous Arterial Spin Labeling (pCASL) has been hampered by B1/B0 inhomogeneities that affect pCASL labeling, background suppression (BS), and the readout sequence. This study aimed to present a whole-cerebrum distortion-free three-dimensional (3D) pCASL sequence at 7T by optimizing pCASL labeling parameters, BS pulses, and an accelerated Turbo-FLASH (TFL) readout. A new set of pCASL labeling parameters (Gave = 0.4 mT/m, Gratio = 14.67) was proposed to avoid interferences in bottom slices while achieving robust labeling efficiency (LE). An OPTIM BS pulse was designed based on the range of B1/B0 inhomogeneities at 7T. A 3D TFL readout with 2D-CAIPIRINHA undersampling (R = 2 × 2) and centric ordering was developed, and the number of segments (Nseg) and flip angle (FA) were varied in simulation to achieve the optimal trade-off between SNR and spatial blurring. In-vivo experiments were performed on 19 subjects. The results showed that the new set of labeling parameters effectively achieved whole-cerebrum coverage by eliminating interferences in bottom slices while maintaining a high LE. The OPTIM BS pulse achieved 33.3% higher perfusion signal in gray matter (GM) than the original BS pulse with a cost of 4.8-fold SAR. Incorporating a moderate FA (8°) and Nseg (2), whole-cerebrum 3D TFL-pCASL imaging was achieved with a 2 × 2 × 4 mm3 resolution without distortion and susceptibility artifacts compared to 3D GRASE-pCASL. In addition, 3D TFL-pCASL showed a good to excellent test-retest repeatability and potential of higher resolution (2 mm isotropic). The proposed technique also significantly improved SNR when compared to the same sequence at 3T and simultaneous multislice TFL-pCASL at 7T. By combining a new set of labeling parameters, OPTIM BS pulse, and accelerated 3D TFL readout, we achieved high resolution pCASL at 7T with whole-cerebrum coverage, detailed perfusion and anatomical information without distortion, and sufficient SNR.

Retrospective motion artifact correction of structural MRI images using deep learning improves the quality of cortical surface reconstructions.

Head motion during MRI acquisition presents significant challenges for neuroimaging analyses. In this work, we present a retrospective motion correction framework built on a Fourier domain motion simulation model combined with established 3D convolutional neural network (CNN) architectures. Quantitative evaluation metrics were used to validate the method on three separate multi-site datasets. The 3D CNN was trained using motion-free images that were corrupted using simulated artifacts. CNN based correction successfully diminished the severity of artifacts on real motion affected data on a separate test dataset as measured by significant improvements in image quality metrics compared to a minimal motion reference image. On the test set of 13 image pairs, the mean peak signal-to-noise-ratio was improved from 31.7 to 33.3 dB. Furthermore, improvements in cortical surface reconstruction quality were demonstrated using a blinded manual quality assessment on the Parkinson's Progression Markers Initiative (PPMI) dataset. Upon applying the correction algorithm, out of a total of 617 images, the number of quality control failures was reduced from 61 to 38. On this same dataset, we investigated whether motion correction resulted in a more statistically significant relationship between cortical thickness and Parkinson's disease. Before correction, significant cortical thinning was found to be restricted to limited regions within the temporal and frontal lobes. After correction, there was found to be more widespread and significant cortical thinning bilaterally across the temporal lobes and frontal cortex. Our results highlight the utility of image domain motion correction for use in studies with a high prevalence of motion artifacts, such as studies of movement disorders as well as infant and pediatric subjects.

Robust single-shot acquisition of high resolution whole brain ASL images by combining time-dependent 2D CAPIRINHA sampling with spatio-temporal TGV reconstruction.

For ASL perfusion imaging in clinical settings the current guidelines recommends pseudo-continuous arterial spin labeling with segmented 3D readout. This combination achieves the best signal to noise ratio with reasonable resolution but is prone to motion artifacts due to the segmented readout. Motion robust single-shot 3D acquisitions suffer from image blurring due to the T2 decay of the sampled signals during the long readout. To tackle this problem, we propose an accelerated 3D-GRASE sequence with a time-dependent 2D-CAIPIRINHA sampling pattern. This has several advantages: First, the single-shot echo trains are shortened by the acceleration factor; Second, the temporal incoherence between measurements is increased; And third, the coil sensitivity maps can be estimated directly from the averaged k-space data. To obtain improved perfusion images from the undersampled time series, we developed a variational image reconstruction approach employing spatio-temporal total-generalized-variation (TGV) regularization. The proposed ASL-TGV method reduced the total acquisition time, improved the motion robustness of 3D ASL data, and the image quality of the cerebral blood flow (CBF) maps compared to those by a standard segmented approach. An evaluation was performed on 5 healthy subjects including intentional movement for 2 subjects. Single-shot whole brain CBF-maps with high resolution 3.1 × 3.1 × 3 mm and image quality can be acquired in 1min 46sec. Additionally high quality CBF- and arterial transit time (ATT) -maps from single-shot multi-post-labeling delay (PLD) data can be gained with the proposed method. This method may improve the robustness of 3D ASL in clinical settings, and may be applied for perfusion fMRI.

Quantification of intracranial arterial blood flow using noncontrast enhanced 4D dynamic MR angiography.

PURPOSE: Noncontrast enhanced dynamic magnetic resonance angiography delineates the pattern of dynamic blood flow of the cerebral vasculature. A model-free solution was proposed to quantify arterial blood flow (aBF) by using the monotonic property of the residual function. THEORY AND METHODS: Analytical simulations and in-vivo studies were performed to evaluate the performance of the proposed method by comparing the aBF values generated from the proposed and conventional singular value decomposition methods. The aBF values were compared with blood flow velocity measured by 2D phase contrast MRI, and compared between balanced steady-state free precession-based radial and spoiled GRE-based Cartesian acquisitions. Hemodynamic parametric maps were generated in 1 patient with arteriovenous malformation. RESULTS: The proposed method generates reliable aBF measurement at different signal-to-noise ratio levels, whereas overestimation/underestimation of aBF was observed when a high/low threshold was applied in the singular value decomposition method. Average aBF in large vascular branches was 214.4 and 214.5 mL/mL/min with radial and Cartesian acquisitions, respectively. Significant correlations were found between aBF and blood flow velocity measured by phase contrast MRI (P = 0.0008), and between Cartesian and radial acquisitions (P < 0.0001). Altered hemodynamics were observed at the lesion site of the arteriovenous malformation patient. CONCLUSION: A robust analytical solution was proposed for quantifying aBF. This model-free method is robust to noise, and its clinical value in the diagnosis of cerebrovascular disorders awaits further evaluation.

Noncontrast-enhanced time-resolved 4D dynamic intracranial MR angiography at 7T: A feasibility study.

BACKGROUND: Arterial spin labeling (ASL) based-noncontrast-enhanced 4D MR angiography (NCE 4D MRA) shows potential in characterizing cerebrovascular hemodynamics in cerebrovascular disorders. Ultrahigh-field theoretically benefits ASL signal with increased inherent signal-to-noise ratio (SNR) and prolonged blood T1 , which may provide improved delineation of vasculature in 4D MRA. PURPOSE: To investigate the feasibility of NCE 4D MRA using 3D Cartesian trajectory and stack-of-stars (SOS) golden angle radial trajectory at 7T. STUDY TYPE: A prospective study. SUBJECTS: Six normal volunteers and eight patients with arteriovenous malformation (AVM). FIELD STRENGTH/SEQUENCE: NCE 4D MRA with Cartesian and radial trajectories were performed at 3T and 7T. ASSESSMENT: Subjective image quality of 4D MRA was evaluated using a 4-point scale by two experienced neuroradiologists. The characterization of AVM components with 4D MRA and DSA was also graded using the Spetzler-Martin grading scale. STATISTICAL TESTS: Cohen's kappa coefficient was calculated to evaluate the agreement between two readers within each 4D MRA technique (Cartesian and Radial). A Wilcoxon signed-rank test was performed to compare the subjective image quality scores of 4D MRA between Cartesian and radial trajectories, and between 7T and 3T, respectively. RESULTS: Good-to-excellent image quality was achieved in 4D MRA with both Cartesian (3.83 ± 0.41) and radial (3.42 ± 0.49) acquisitions in healthy volunteers at 7T. However, markedly reduced scan time was needed with radial acquisition. 4D MRA at 7T (3.31 ± 0.59) shows better delineation of AVM lesion features, especially the vein drainage, compared with that of 3T (2.83 ± 0.75), although no statistical significance was achieved (P = 0.180). DATA CONCLUSION: The feasibility of ASL based 4D MRA at 7T with Cartesian and SOS golden angle radial acquisition was demonstrated. The clinical evaluation of 4D MRA in AVMs between 3T and 7T suggested 7T 4D MRA images acquired with radial acquisition demonstrate excellent delineation of AVM features, especially the draining veins. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2017.

Arterial spin labeling MRI is able to detect early hemodynamic changes in diabetic nephropathy.

PURPOSE: To investigate whether arterial spin labeling (ASL) MRI could detect renal hemodynamic impairment in diabetes mellitus (DM) along different stages of chronic kidney disease (CKD). MATERIALS AND METHODS: Three Tesla (3T) ASL-MRI was performed to evaluate renal blood flow (RBF) in 91 subjects (46 healthy volunteers and 45 type 2 diabetic patients). Patients were classified according to their estimated glomerular filtration rate (eGFR) as group I (eGFR > 60 mL/min/1.73 m2 ), group II (60 ≥ eGFR>30 mL/min/1.73 m2 ), or group III (eGFR ≤ 30 mL/min/1.73 m2 ), to determine differences depending on renal function. Studies were performed at 3T using a 12-channel flexible body array combined with the spine array coil as receiver. RESULTS: A 28% reduction in cortical RBF was seen in diabetics in comparison with healthy controls (185.79 [54.60] versus 258.83 [37.96] mL/min/100 g, P < 3 × 10-6 ). Differences were also seen between controls and diabetic patients despite normal eGFR and absence of overt albuminuria (RBF [mL/min/100 g]: controls=258.83 [37.96], group I=208.89 [58.83], P = 0.0018; eGFR [mL/min/1.73 m2 ]: controls = 95.50 [12.60], group I = 82.00 [20.76], P > 0.05; albumin-creatinine ratio [mg/g]: controls = 3.50 [4.45], group I = 17.50 [21.20], P > 0.05). A marked decrease in RBF was noted a long with progression of diabetic nephropathy (DN) through the five stages of CKD (χ2 = 43.58; P = 1.85 × 10-9 ). Strong correlation (r = 0.62; P = 4 × 10-10 ) was obtained between RBF and GFR estimated by cystatin C. CONCLUSION: ASL-MRI is able to quantify early renal perfusion impairment in DM, as well as changes according to different CKD stages of DN. In addition, we demonstrated a correlation of RBF quantified by ASL and GFR estimated by cystatin C. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1810-1817.

High Resolution Multi-delay Arterial Spin Labeling with Transformer based Denoising for Pediatric Perfusion MRI.

Multi-delay arterial spin labeling (MDASL) can quantitatively measure cerebral blood flow (CBF) and arterial transit time (ATT), which is particularly suitable for pediatric perfusion imaging. Here we present a high resolution (iso-2mm) MDASL protocol and performed test-retest scans on 21 typically developing children aged 8 to 17 years. We further proposed a Transformer-based deep learning (DL) model with k-space weighted image average (KWIA) denoised images as reference for training the model. The performance of the model was evaluated by the SNR of perfusion images, as well as the SNR, bias and repeatability of the fitted CBF and ATT maps. The proposed method was compared to several benchmark methods including KWIA, joint denoising and reconstruction with total generalized variation (TGV) regularization, as well as directly applying a pretrained Transformer model on a larger dataset. The results show that the proposed Transformer model with KWIA reference can effectively denoise multi-delay ASL images, not only improving the SNR for perfusion images of each delay, but also improving the SNR for the fitted CBF and ATT maps. The proposed method also improved test-retest repeatability of whole-brain perfusion measurements. This may facilitate the use of MDASL in neurodevelopmental studies to characterize typical and aberrant brain development.

Age-Related Decline in Blood-Brain Barrier Function is More Pronounced in Males than Females in Parietal and Temporal Regions.

The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8 to 92 years old, using a non-invasive diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI technique. We found that the pattern of BBB kw decline with aging varies across brain regions. Moreover, results from our DP-pCASL technique revealed a remarkable decline in BBB kw beginning in the early 60s, which was more pronounced in males. In addition, we observed sex differences in parietal and temporal regions. Our findings provide in vivo results demonstrating sex differences in the decline of BBB function with aging, which may serve as a foundation for future investigations into perfusion and BBB function in neurodegenerative and other brain disorders.

Spontaneous cerebrovascular reactivity at rest in older adults with and without mild cognitive impairment and memory deficits.

Background: Older adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI. This study examined if spontaneous CVR is associated with MCI and memory impairment. Methods: 161 older adults free of dementia or major neurological/psychiatric disorders were recruited. Participants underwent clinical interviews, cognitive testing, venipuncture for Alzheimer's biomarkers, and brain MRI. Spontaneous CVR was quantified during 5 minutes of rest. Results: Whole brain CVR was negatively associated with age, but not MCI. Lower CVR in the parahippocampal gyrus (PHG) was found in participants with MCI and was linked to worse memory performance on memory tests. Results remained significant after adjusting for Alzheimer's biomarkers and vascular risk factors. Conclusion: Spontaneous CVR deficits in the PHG are observed in older adults with MCI and memory impairment, indicating medial temporal microvascular dysfunction's role in cognitive decline.

Neurofluids and the glymphatic system: anatomy, physiology, and imaging.

First described in 2012, the glymphatic system is responsible for maintaining homeostasis within the central nervous system, including nutrient delivery, waste clearance, and consistency of the ionic microenvironment. It is comprised of glial cells and barrier systems that modulate neurofluid production, circulation, and exchange. Experimental interrogation of neurofluid dynamics is restricted to ex vivo and in vitro studies in animals and humans, therefore diagnostic imaging plays an important role in minimally invasive evaluation. This review article will synthesize current knowledge and theories regarding neurofluid circulation and implications for neuroimaging. First, we will discuss the anatomy of the neurogliovascular unit, including paravascular and perivascular pathways of fluid exchange. In addition, we will summarize the structure and function of barrier systems including the blood-brain, blood-cerebrospinal fluid, and brain-cerebrospinal fluid barriers. Next, we will mention physiologic factors that yield normal variations in neurofluid circulation, and how various disease pathologies can disrupt glymphatic drainage pathways. Lastly, we will cover the spectrum of diagnostic imaging and interventional techniques with relevance to glymphatic structure, flow, and function. We conclude by highlighting current barriers and future directions for translational imaging and applications to neurologic disorders.

Transformer based deep learning denoising of single and multi-delay 3D Arterial Spin Labeling.

Purpose: To present a Swin Transformer-based deep learning (DL) model for denoising of single-delay and multi-delay 3D arterial spin labeling (ASL) and compare its performance with convolutional neural network (CNN) methods. Methods: Swin Transformer and CNN-based spatial denoising models were developed for single-delay ASL. The models were trained on 59 subjects (104 scans) and tested on 44 subjects (57 scans) from 3 different vendors. Spatiotemporal denoising models were developed using another dataset (6 subjects, 10 scans) of multi-delay ASL. A range of input conditions was tested for denoising single and multi-delay ASL respectively. The performance was evaluated using similarity metrics, spatial signal-to-noise ratio (SNR) and quantification accuracy of cerebral blood flow (CBF) and arterial transit time (ATT). Results: Swin Transformer outperformed CNN-based networks, whereas pseudo-3D models showed better performance than 2D models for denoising single-delay ASL. The similarity metrics and image quality (SNR) improved with more slices in pseudo-3D models, and further improved when using M0 as input but introduced greater biases for CBF quantification. Pseudo-3D models with 3 slices as input achieved optimal balance between SNR and accuracy, which can be generalized to different vendors. For multi-delay, spatiotemporal denoising models had better performance than spatial-only models with reduced biases in fitted CBF and ATT maps. Conclusions: Swin Transformer DL models provided better performance than CNN methods for denoising both single and multi-delay 3D ASL data. The proposed model offers flexibility to improve image quality and/or reduce scan time for 3D ASL to facilitate its clinical use.

Whole-Cerebrum distortion-free three-dimensional pseudo-Continuous Arterial Spin Labeling at 7T.

Fulfilling potentials of ultrahigh field for pseudo-Continuous Arterial Spin Labeling (pCASL) has been hampered by B1/B0 inhomogeneities that affect pCASL labeling, background suppression (BS), and the readout sequence. This study aimed to present a whole-cerebrum distortion-free three-dimensional (3D) pCASL sequence at 7T by optimizing pCASL labeling parameters, BS pulses, and an accelerated Turbo-FLASH (TFL) readout. A new set of pCASL labeling parameters (Gave=0.4mT/m, Gratio=14.67) was proposed to avoid interferences in bottom slices while achieving robust labeling efficiency (LE). An OPTIM BS pulse was designed based on the range of B1/B0 inhomogeneities at 7T. A 3D TFL readout with 2D-CAIPIRINHA undersampling (R=2×2) and centric ordering was developed, and the number of segments (Nseg) and flip angle (FA) were varied in simulation to achieve the optimal trade-off between SNR and spatial blurring. In-vivo experiments were performed on 19 subjects. The results showed that the new set of labeling parameters effectively achieved whole-cerebrum coverage by eliminating interferences in bottom slices while maintaining a high LE. The OPTIM BS pulse achieved 33.3% higher perfusion signal in gray matter (GM) than the original BS pulse with a cost of 4.8-fold SAR. Incorporating a moderate FA (8 ° ) and Nseg (2), whole-cerebrum 3D TFL-pCASL imaging was achieved with a 2×2×4 mm 3 resolution without distortion and susceptibility artifacts compared to 3D GRASE-pCASL. In addition, 3D TFL-pCASL showed a good to excellent test-retest repeatability and potential of higher resolution (2 mm isotropic). The proposed technique also significantly improved SNR when compared to the same sequence at 3T and simultaneous multislice TFL-pCASL at 7T. By combining a new set of labeling parameters, OPTIM BS pulse, and accelerated 3D TFL readout, we achieved high resolution pCASL at 7T with whole-cerebrum coverage, detailed perfusion and anatomical information without distortion, and sufficient SNR.

Depression, stress and regional cerebral blood flow.

Decreased cerebral blood flow (CBF) may be an important mechanism associated with depression. In this study we aimed to determine if the association of CBF and depression is dependent on current level of depression or the tendency to experience depression over time (trait depression), and if CBF is influenced by depression-related factors such as stressful life experiences and antidepressant medication use. CBF was measured in 254 participants from the Amish Connectome Project (age 18-76, 99 men and 154 women) using arterial spin labeling. All participants underwent assessment of symptoms of depression measured with the Beck Depression Inventory and Maryland Trait and State Depression scales. Individuals diagnosed with a unipolar depressive disorder had significantly lower average gray matter CBF compared to individuals with no history of depression or to individuals with a history of depression that was in remission at time of study. Trait depression was significantly associated with lower CBF, with the associations strongest in cingulate gyrus and frontal white matter. Use of antidepressant medication and more stressful life experiences were also associated with significantly lower CBF. Resting CBF in specific brain regions is associated with trait depression, experience of stressful life events, and current antidepressant use, and may provide a valuable biomarker for further studies.

Layer-dependent multiplicative effects of spatial attention on contrast responses in human early visual cortex.

Attention mechanisms at different cortical layers of human visual cortex remain poorly understood. Using submillimeter-resolution fMRI at 7 Tesla, we investigated the effects of top-down spatial attention on the contrast responses across different cortical depths in human early visual cortex. Gradient echo (GE) T2* weighted BOLD signal showed an additive effect of attention on contrast responses across cortical depths. Compared to the middle cortical depth, attention modulation was stronger in the superficial and deep depths of V1, and also stronger in the superficial depth of V2 and V3. Using ultra-high resolution (0.3 mm in-plane) balanced steady-state free precession (bSSFP) fMRI, a multiplicative scaling effect of attention was found in the superficial and deep layers, but not in the middle layer of V1. Attention modulation of low contrast response was strongest in the middle cortical depths, indicating baseline enhancement or contrast gain of attention modulation on feedforward input. Finally, the additive vs. scaling effect of attention from GE-EPI and bSSFP signals can be explained by stronger nonlinearity of BOLD signals from large than small blood vessels, suggesting multiplicative effect of attention on neural activity. These findings support that top-down spatial attention mainly operates through feedback connections from higher order cortical areas, and a distinct mechanism of attention may also be associated with feedforward input through subcortical pathway.

Cerebroarterial pulsatility and resistivity indices are associated with cognitive impairment and white matter hyperintensity in elderly subjects: A phase-contrast MRI study.

Increased cerebroarterial pulsations are thought to be contributing factors in microvascular damage and cognitive impairment. In this study, we assessed the utility of two-dimensional (2D) phase-contrast MRI (PC-MRI) in quantifying cerebroarterial pulsations and evaluated the associations of pulsatile and non-pulsatile hemodynamic measures with cognitive performance and white matter hyperintensities (WMH). Neurocognitive assessments on 50 elderly subjects were performed using clinical dementia rating (CDR) and Montreal cognitive assessment (MoCA). An electrocardiogram-gated 2D PC-MRI sequence was used to calculate mean flow rate, pulsatility index (PI), and resistivity index (RI) of the internal carotid artery. For each subject, whole brain global cerebral blood flow (gCBF) and relative WMH volume were also quantified. Elevated RI was significantly associated with reduced cognitive performance quantified using MoCA (p = 0.04) and global CDR (p = 0.02). PI and RI were both significantly associated with relative WMH volume (p = 0.01, p < 0.01, respectively). However, non-pulsatile hemodynamic measures were not associated with cognitive impairment or relative WMH volume. This study showed that the cerebroarterial pulsatile measures obtained using PC-MRI have stronger association with the measures of cognitive impairment compared to global blood flow measurement and as such, might be useful as potential biomarkers of cerebrovascular dysfunction in preclinical populations.

A novel technique for accurate electrode placement over cortical targets for transcranial electrical stimulation (tES) clinical trials.

Objective. We present an easy-to-implement technique for accurate electrode placement over repeated transcranial electrical stimulation (tES) sessions across participants and time. tES is an emerging, non-invasive neuromodulation technique that delivers electrical stimulation using scalp electrodes.Approach.The tES electrode placement technique was developed during an exploratory clinical trial aimed at targeting a specific MNI-atlas cortical coordinate inN= 59 depressed participants (32 F, mean age: 31.1 ± 8.3 SD). Each participant completed 12 sessions of active or sham stimulation, administered using high-definition (HD) or conventional sized electrode montages placed according to the proposed technique. Neuronavigation data measuring the distances between the identified and the intended stimulation site, simulations, and cerebral blood flow (CBF) data at baseline and post-treatment were acquired to evaluate the targeting characteristics of the proposed technique.Main results.Neuronavigation measurements indicate accurate electrode placement to within 1 cm of the stimulation target on average across repeated sessions. Simulations predict that these placement characteristics result in minimal electric field differences at the stimulation target (>0.90 correlation, and <10% change in the modal electric field and targeted volume). Additionally, significant changes in %CBF (relative to baseline) under the stimulation target in the active stimulation group relative to sham confirmed that the proposed placement technique introduces minimal bias in the spatial location of the cortical coordinate ultimately targeted. Finally, we show proof of concept that the proposed technique provides similar accuracy of electrode placement at other cortical targets.Significance.For voxel-level cortical targets, existing techniques based on cranial landmarks are suboptimal. Our results show that the proposed electrode placement approach provides high consistency for the accurate targeting of such specific cortical regions. Overall, the proposed technique now enables the accurate targeting of locations not accessible with the existing 10-20 system such as scalp-projections of clinically-relevant cortical coordinates identified by brain mapping studies. Clinical trial ID: NCT03556124.

Cerebral perfusion is associated with blast exposure in military personnel without moderate or severe TBI.

Due to the use of improvised explosive devices, blast exposure and mild traumatic brain injury (mTBI) have become hallmark injuries of the Iraq and Afghanistan wars. Although the mechanisms of the effects of blast on human neurobiology remain active areas of investigation, research suggests that the cerebrovasculature may be particularly vulnerable to blast via molecular processes that impact cerebral blood flow. Given that recent work suggests that blast exposure, even without a subsequent TBI, may have negative consequences on brain structure and function, the current study sought to further understand the effects of blast exposure on perfusion. One hundred and eighty military personnel underwent pseudo-continuous arterial spin labeling (pCASL) imaging and completed diagnostic and clinical interviews. Whole-brain analyses revealed that with an increasing number of total blast exposures, there was significantly increased perfusion in the right middle/superior frontal gyri, supramarginal gyrus, lateral occipital cortex, and posterior cingulate cortex as well as bilateral anterior cingulate cortex, insulae, middle/superior temporal gyri and occipital poles. Examination of other neurotrauma and clinical variables such as close-range blast exposures, mTBI, and PTSD yielded no significant effects. These results raise the possibility that perfusion may be an important neural marker of brain health in blast exposure.

Dynamics of the cerebral blood flow response to brief neural activity in human visual cortex.

The blood oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal depends on an interplay of cerebral blood flow (CBF), oxygen metabolism, and cerebral blood volume. Despite wide usage of BOLD fMRI, it is not clear how these physiological components create the BOLD signal. Here, baseline CBF and its dynamics evoked by a brief stimulus (2 s) in human visual cortex were measured at 3T. We found a stereotypical CBF response: immediate increase, rising to a peak a few second after the stimulus, followed by a significant undershoot. The BOLD hemodynamic response function (HRF) was also measured in the same session. Strong correlations between HRF and CBF peak responses indicate that the flow responses evoked by neural activation in nearby gray matter drive the early HRF. Remarkably, peak CBF and HRF were also strongly modulated by baseline perfusion. The CBF undershoot was reliable and significantly correlated with the HRF undershoot. However, late-time dynamics of the HRF and CBF suggest that oxygen metabolism can also contribute to the HRF undershoot. Combined measurement of the CBF and HRF for brief neural activation is a useful tool to understand the temporal dynamics of neurovascular and neurometabolic coupling.

Collateral perfusion using arterial spin labeling in symptomatic versus asymptomatic middle cerebral artery stenosis.

The purpose was to assess the difference of collaterals in symptomatic versus asymptomatic patients with unilateral middle cerebral artery (MCA) stenosis by comparing cerebral blood flow (CBF) at two post labeling delays (PLD) using three-dimensional pseudo-continuous arterial spin labeling (3D pCASL). Eighty-one patients (49 symptomatic and 32 asymptomatic) with unilateral MCA stenosis ≥50% who underwent pCASL with two PLDs were included. Mean CBF and CBF subtraction images between two PLDs of MCA territories were compared in symptomatic and asymptomatic groups, respectively. Compared with the asymptomatic group, patients with symptomatic MCA stenosis had significantly lower CBF in the MCA territory of stenotic side at each PLD. The CBF of stenotic territory showed greater increase than that of normal side from PLD 1.5 to 2.5 s. The CBF of asymptomatic MCA territory increased similarly with that of symptomatic MCA territory from PLD of 1.5 to 2.5 s in stenotic side, while symptomatic patients experienced significantly slower antegrade flow. On CBF subtraction images, asymptomatic patients showed larger volume of differences between PLD of 1.5 and 2.5 s compared with those of symptomatic patients ( p = 0.037). The results suggest that more robust collateral perfusion on two-delay 3D pCASL is present in asymptomatic patients compared with symptomatic patients.

Hypercapnia increases brain viscoelasticity.

Brain function, the brain's metabolic activity, cerebral blood flow (CBF), and intracranial pressure are intimately linked within the tightly autoregulated regime of intracranial physiology in which the role of tissue viscoelasticity remains elusive. We applied multifrequency magnetic resonance elastography (MRE) paired with CBF measurements in 14 healthy subjects exposed to 5-min carbon dioxide-enriched breathing air to induce cerebral vasodilatation by hypercapnia. Stiffness and viscosity as quantified by the magnitude and phase angle of the complex shear modulus, |G*| and ϕ, as well as CBF of the whole brain and 25 gray matter sub-regions were analyzed prior to, during, and after hypercapnia. In all subjects, whole-brain stiffness and viscosity increased due to hypercapnia by 3.3 ± 1.9% and 2.0 ± 1.1% which was accompanied by a CBF increase of 36 ± 15%. Post-hypercapnia, |G*| and ϕ reduced to normal values while CBF decreased by 13 ± 15% below baseline. Hypercapnia-induced viscosity changes correlated with CBF changes, whereas stiffness changes did not. The MRE-measured viscosity changes correlated with blood viscosity changes predicted by the Fåhræus-Lindqvist model and microvessel diameter changes from the literature. Our results suggest that brain viscoelastic properties are influenced by microvessel blood flow and blood viscosity: vasodilatation and increased blood viscosity due to hypercapnia result in an increase in MRE values related to viscosity.