Association of Wearable Device-Measured Step Volume and Variability With Blood Pressure in Older Chinese Adults: Mobile-Based Longitudinal Observational Study.

BACKGROUND: The paucity of evidence on longitudinal and consecutive recordings of physical activity (PA) and blood pressure (BP) under real-life conditions and their relationships is a vital research gap that needs to be addressed. OBJECTIVE: This study aims to (1) investigate the short-term relationship between device-measured step volume and BP; (2) explore the joint effects of step volume and variability on BP; and (3) examine whether the association patterns between PA and BP varied across sex, hypertension status, and chronic condition status. METHODS: This study used PA data of a prospective cohort of 3070 community-dwelling older adults derived from a mobile health app. Daily step counts, as a proxy of step volume, were derived from wearable devices between 2018 and 2022 and categorized into tertiles (low, medium, and high). Step variability was assessed using the SD of daily step counts. Consecutive daily step count recordings within 0 to 6 days preceding each BP measurement were analyzed. Generalized estimation equation models were used to estimate the individual and joint associations of daily step volume and variability with BP. Stratified analyses by sex, the presence of hypertension, and the number of morbidities were further conducted. RESULTS: A total of 3070 participants, with a median age of 72 (IQR 67-77) years and 71.37% (2191/3070) women, were included. Participants walked a median of 7580 (IQR 4972-10,653) steps and 5523 (IQR 3590-7820) meters per day for a total of 592,597 person-days of PA monitoring. Our results showed that higher levels of daily step volume were associated with lower BP (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure). Compared with participants with low step volume (daily step counts <6000/d) and irregular steps, participants with high step volume (≥9500/d) and regular steps showed the strongest decrease in systolic BP (-1.69 mm Hg, 95% CI -2.2 to -1.18), while participants with medium step volume (6000/d to <9500/d) and regular steps were associated with the lowest diastolic BP (-1.067 mm Hg, 95% CI -1.379 to -0.755). Subgroup analyses indicated generally greater effects on women, individuals with normal BP, and those with only 1 chronic disease, but the effect pattern was varied and heterogeneous between participants with different characteristics. CONCLUSIONS: Increased step volume demonstrated a substantial protective effect on BP among older adults with chronic conditions. Furthermore, the beneficial association between step volume and BP was enhanced by regular steps, suggesting potential synergistic protective effects of both increased step volume and step regularity. Targeting both step volume and variability through PA interventions may yield greater benefits in BP control, particularly among participants with hypertension and a higher chronic disease burden.

[Association between insomnia and type 2 diabetes: A two-sample Mendelian rando-mization study].

OBJECTIVE: To explore the robust relationship between insomnia and type 2 diabetes mellitus by two-sample Mendelian randomization analysis to overcome confounding factors and reverse causality in observational studies. METHODS: We identified strong, independent single nucleotide polymorphisms (SNPs) of insomnia from the most up to date genome wide association studies (GWAS) within European ancestors and applied them as instrumental variable to GWAS of type 2 diabetes mellitus. After excluding SNPs that were significantly associated with smoking, physical activity, alcohol consumption, educational attainment, obesity, or type 2 diabetes mellitus, we assessed the impact of insomnia on type 2 diabetes mellitus using inverse variance weighting (IVW) method. Weighted median and MR-Egger regression analysis were also conducted to test the robustness of the association. We calculated the F statistic of the selected SNPs to test the applicability of instrumental variable and F statistic over than ten indicated that there was little possibility of bias of weak instrumental variables. We further examined the existence of pleiotropy by testing whether the intercept term in MR-Egger regression was significantly different from zero. In addition, the leave-one-out method was used for sensitivity analysis to verify the stability and reliability of the results. RESULTS: We selected 248 SNPs independently associated with insomnia at the genome-wide level (P<5×10-8) as a preliminary candidate set of instrumental variables. After clumping based on the reference panel from 1000 Genome Project and removing the potential pleiotropic SNPs, a total of 167 SNPs associated with insomnia were included as final instrumental variables. The F statistic of this study was 39. 74, which was in line with the relevance assumption of Mendelian randomization. IVW method showed insomnia was associated with higher risk of type 2 diabetes mellitus that po-pulation with insomnia were 1. 14 times more likely to develop type 2 diabetes mellitus than those without insomnia (95% CI: 1.09-1.21, P<0.001). The weighted median estimator (WME) method and MR-Egger regression showed similar causal effect of insomnia on type 2 diabetes mellitus. And MR-Egger regression also showed that the effect was less likely to be triggered by pleiotropy. Sensitivity analyses produced directionally similar estimates. CONCLUSION: Insomnia is a risk factor of type 2 diabetes mellitus, which has positively effects on type 2 diabetes mellitus. Our study provides further rationale for indivi-duals at risk for diabetes to keep healthy lifestyle.

Tumor-Derived PD-L1+ Exosomes with Natural Inflammation Tropism for Psoriasis-Targeted Treatment.

Psoriasis is a chronic inflammatory disease whose etiology is directly related to the dysregulation of cutaneous immune homeostasis. However, how to finely modulate the skin immune microenvironment to restore homeostasis remains an important challenge. Inspired by the natural attribute of tumor exosomes in the immune escape, the tumor-derived exosomes as an active targeting nanoplatform for the effective treatment of inflammatory skin disorder were first reported. As keratinocytes and immune cells express high PD-1 during the onset of psoriasiform skin inflammation, the PD-L1-positive exosomes derived from melanoma cells carrying pristimerin with extremely anti-inflammatory potential were yielded to treat psoriasis. The PD-L1+ exosomes carrying pristimerin were characterized, and the cellular uptake was performed to evaluate the PD-1 target capability. The anti-inflammatory action of PD-L1+ exosomes carrying pristimerin was observed in both in vitro and in vivo models of psoriasis. Our exosomes substantially increased pristimerin uptake with CD4+ T cells and keratinocytes, significantly inhibited the proliferation of Th17 cells, and promoted Treg differentiation in a psoriasis-like model. Obviously, PD-L1+ exosomes carrying pristimerin significantly and safely reversed imiquimod (IMQ)-induced psoriasis in mice, indicated by reducing epidermal thickness, decreasing plaque formation, and suppressed excessive inflammatory response, due to its dual targeting of both CD4+ T cells and keratinocytes gathering around the lesion. The inflammatory cell infiltration and pro-inflammatory cytokine production in psoriasis were suppressed by our engineered exosomes. Besides, PD-L1+ exosomes carrying pristimerin treatment alleviated ferroptosis-related changes in psoriatic skin, thereby dampening excessive inflammation and, in turn, decreasing the abnormal proliferation of keratinocytes in psoriatic lesions. This study demonstrates that our engineered exosomes can not only act as a treat-to-target strategy for psoriasis treatment but also provide insight in clinical application of inflammatory disorders.

Disease patterns of coronary heart disease and type 2 diabetes harbored distinct and shared genetic architecture.

BACKGROUND: Coronary heart disease (CHD) and type 2 diabetes (T2D) are two complex diseases with complex interrelationships. However, the genetic architecture of the two diseases is often studied independently by the individual single-nucleotide polymorphism (SNP) approach. Here, we presented a genotypic-phenotypic framework for deciphering the genetic architecture underlying the disease patterns of CHD and T2D. METHOD: A data-driven SNP-set approach was performed in a genome-wide association study consisting of subpopulations with different disease patterns of CHD and T2D (comorbidity, CHD without T2D, T2D without CHD and all none). We applied nonsmooth nonnegative matrix factorization (nsNMF) clustering to generate SNP sets interacting the information of SNP and subject. Relationships between SNP sets and phenotype sets harboring different disease patterns were then assessed, and we further co-clustered the SNP sets into a genetic network to topologically elucidate the genetic architecture composed of SNP sets. RESULTS: We identified 23 non-identical SNP sets with significant association with CHD or T2D (SNP-set based association test, P < 3.70 × [Formula: see text]). Among them, disease patterns involving CHD and T2D were related to distinct SNP sets (Hypergeometric test, P < 2.17 × [Formula: see text]). Accordingly, numerous genes (e.g., KLKs, GRM8, SHANK2) and pathways (e.g., fatty acid metabolism) were diversely implicated in different subtypes and related pathophysiological processes. Finally, we showed that the genetic architecture for disease patterns of CHD and T2D was composed of disjoint genetic networks (heterogeneity), with common genes contributing to it (pleiotropy). CONCLUSION: The SNP-set approach deciphered the complexity of both genotype and phenotype as well as their complex relationships. Different disease patterns of CHD and T2D share distinct genetic architectures, for which lipid metabolism related to fibrosis may be an atherogenic pathway that is specifically activated by diabetes. Our findings provide new insights for exploring new biological pathways.

A novel sequence for simultaneous measurement of whole-brain static and dynamic MRA, intracranial vessel wall image, and T1 -weighted structural brain MRI.

PURPOSE: To propose a highly time-efficient imaging technique named improved simultaneous noncontrast angiography and intraplaque hemorrhage (iSNAP) for simultaneous assessment of lumen, vessel wall, and blood flow in intracranial arteries. METHODS: iSNAP consists of pulsed arterial spin labeling preparations and 3D golden angle radial acquisition. Images were reconstructed by k-space weighted image contrast (KWIC) method with optimized data-sharing strategies. Dynamic MRA for blood flow assessment was obtained from iSNAP by reconstruction at multiple inversion times and image subtraction, static MRA by both image subtraction approach and phase-sensitive inversion recovery technique, and vessel wall images by both reconstruction at zero-crossing time-point of blood and phase-sensitive inversion recovery. A T1 -weighted brain MRI was also reconstructed from iSNAP. Preliminary comparison of iSNAP against the dedicated dynamic MRA sequence 4D-TRANCE, MRA/vessel wall imaging sequence SNAP, and vessel wall imaging sequence T1 -weighted VISTA was performed in healthy volunteers and patients. RESULTS: iSNAP has whole-brain coverage and takes ~6.5 min. The dedicated reconstruction strategies are feasible for each iSNAP image contrast and beneficial for image SNR. iSNAP-dynamic MRA yields similar dynamic flow information as 4D-TRANCE and allows more flexible temporal resolution. The 2 types of iSNAP static MRA images complement each other in characterizing both proximal large arteries and distal small arteries. Depiction of vessel wall lesions in iSNAP vessel wall images is better than SNAP and may be similar to T1 -weighted VISTA, although the images are slightly blurred. CONCLUSION: iSNAP provides a time-efficient evaluation of intracranial arteries and may have great potential for comprehensive assessment of intracranial vascular conditions using a single sequence.

Excess Heritability Contribution of Alcohol Consumption Variants in the "Missing Heritability" of Type 2 Diabetes Mellitus.

We aim to compare the relative heritability contributed by variants of behavior-related environmental phenotypes and elucidate the role of these factors in the conundrum of "missing heritability" of type 2 diabetes. Methods: We used Linkage-Disequilibrium Adjusted Kinships (LDAK) and LDAK-Thin models to calculate the relative heritability of each variant and compare the relative heritability for each phenotype. Biological analysis was carried out for the phenotype whose variants made a significant contribution. Potential hub genes were prioritized based on topological parameters of the protein-protein interaction network. We included 16 behavior-related phenotypes and 2607 valid variants. In the LDAK model, we found the variants of alcohol consumption and caffeine intake were identified as contributing higher relative heritability than that of the random variants. Compared with the relative expected heritability contributed by the variants associated with type 2 diabetes, the relative expected heritability contributed by the variants associated with these two phenotypes was higher. In the LDAK-Thin model, the relative heritability of variants of 11 phenotypes was statistically higher than random variants. Biological function analysis showed the same distributions among type 2 diabetes and alcohol consumption. We eventually screened out 31 hub genes interacting intensively, four of which were validated and showed the upregulated expression pattern in blood samples seen in type 2 diabetes cases. Conclusion: We found that alcohol consumption contributed higher relative heritability. Hub genes may influence the onset of type 2 diabetes by a mediating effect or a pleiotropic effect. Our results provide new insight to reveal the role of behavior-related factors in the conundrum of "missing heritability" of type 2 diabetes.

Self-calibrating wave-encoded 3D turbo spin echo imaging using subspace model based autofocusing.

PURPOSE: To develop a self-calibrating approach for the estimation of wave point spread function (PSF) and coil sensitivities from the subsampled wave-encoded k-space, and evaluate its performance for wave-encoded 3D turbo spin echo (TSE) imaging. METHODS: A low rank subspace parametric model was demonstrated in simulation to improve the representation for practical wave encoding k-space trajectories with aperiodicity, and an autofocus metric for the entire imaging volume was used to calibrate the wave PSF in a 2-stage manner from coarse to refined estimation. The coil sensitivities can be extracted from the shifted central region of wave PSF corrected subsampled k-space, and further used with wave PSF for wave-encoded parallel imaging (PI) reconstruction. The wave encoding gradients were integrated into the 3D TSE sequence considering eddy current reduction aspects and maintaining of the Carr-Purcell-Meiboom-Gill condition. Phantom and in vivo brain experiments were performed to evaluate the accuracy of wave PSF self-calibration and to compare the PI reconstruction performance between wave and Cartesian encoding scheme. RESULTS: The self-calibrated wave PSF, estimated from different k-space undersampling patterns can robustly correct the wave encoding induced image artifacts given sufficient central autocalibration data. The self-calibrating wave-encoded PI reconstruction has demonstrated its improved performance in reduced aliasing artifacts and noise amplification in comparison to the Cartesian-encoded PI reconstruction results for 3D TSE imaging. CONCLUSION: The proposed self-calibrating wave-encoded method allows robust calibration of wave PSF and coil sensitivities from the subsampled k-space, and improves the overall image quality for accelerated 3D TSE imaging.

Analyzing Functional Pathways and constructing gene-gene network for Narcolepsy based on candidate genes.

Aims: To investigate the interactions among narcolepsy-associated genes and reveal the pathways these genes involved through bioinformatics analyses. Methods: The study was performed with the following steps: 1) Selected the previously discovered narcolepsy risk genes through literature review, 2) pathway enrichment analysis, and construction of gene-gene and protein-protein interaction (PPI) networks for narcolepsy. Results: 1) GO analysis revealed the positive regulation of interferon-gamma production as the most enriched terms in biological process, and C-C chemokine receptor activity as the most enriched term in molecular function, 2) KEGG pathway enrichment analysis revealed selective enrichment of genes in cytokine-cytokine receptor interaction signaling pathways, and 3) five hub genes were identified (IFNAR1, IL10RB, DNMT1, TNFSF4 and NFATC2). Conclusion: The bioinformatics results provide new insights into the molecular pathogenesis of narcolepsy and the identification of potential therapeutic targets for narcolepsy treatment.

Accelerated multi-contrast high isotropic resolution 3D intracranial vessel wall MRI using a tailored k-space undersampling and partially parallel reconstruction strategy.

OBJECTIVE: To develop a 3D multi-contrast IVW protocol with 0.5-mm isotropic resolution and a scan time of 5 min per sequence. MATERIALS AND METHODS: Pre-contrast T1w VISTA, DANTE prepared PDw VISTA, SNAP, and post-contrast T1w VISTA were accelerated using cartesian undersampling with target ordering method (CUSTOM) and self-supporting tailored k-space estimation for parallel imaging reconstruction (STEP). CUSTOM + STEP IVW was compared to full-sample IVW, SENSE-accelerated IVW, and CUSTOM + zero-filled Fourier reconstruction in normal volunteers and subjects with intracranial atherosclerotic disease (ICAD). Image quality, vessel delineation, CSF suppression, and blood suppression were compared. RESULTS: CUSTOM + STEP vessel wall delineation was comparable to full-sample IVW and better than SENSE IVW for vessel wall delineation on T1w VISTA and luminal contrast on SNAP. Average image quality and wall depiction were significantly improved using STEP reconstruction compared with zero-filled Fourier reconstruction, with no significant difference in CSF or blood suppression. CONCLUSIONS: CUSTOM + STEP allowed multi-contrast 3D 0.5-mm isotropic IVW within 30 min. Although some quantitative and qualitative scores for CUSTOM - STEP were lower than fully sampled IVW, CUSTOM + STEP provided comparable vessel wall delineation as full-sample IVW and was superior to SENSE. CUSTOM + STEP IVW was well tolerated by patients and showed good delineation of ICAD plaque.

Carotid Intraplaque Hemorrhage Imaging with Quantitative Vessel Wall T1 Mapping: Technical Development and Initial Experience.

Purpose To develop a three-dimensional (3D) high-spatial-resolution time-efficient sequence for use in quantitative vessel wall T1 mapping. Materials and Methods A previously described sequence, simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) imaging, was extended by introducing 3D golden angle radial k-space sampling (GOAL-SNAP). Sliding window reconstruction was adopted to reconstruct images at different inversion delay times (different T1 contrasts) for voxelwise T1 fitting. Phantom studies were performed to test the accuracy of T1 mapping with GOAL-SNAP against a two-dimensional inversion recovery (IR) spin-echo (SE) sequence. In vivo studies were performed in six healthy volunteers (mean age, 27.8 years ± 3.0 [standard deviation]; age range, 24-32 years; five male) and five patients with atherosclerosis (mean age, 66.4 years ± 5.5; range, 60-73 years; five male) to compare T1 measurements between vessel wall sections (five per artery) with and without intraplaque hemorrhage (IPH). Statistical analyses included Pearson correlation coefficient, Bland-Altman analysis, and Wilcoxon rank-sum test with data permutation by subject. Results Phantom T1 measurements with GOAL-SNAP and IR SE sequences showed excellent correlation (R2 = 0.99), with a mean bias of -25.8 msec ± 43.6 and a mean percentage error of 4.3% ± 2.5. Minimum T1 was significantly different between sections with IPH and those without it (mean, 371 msec ± 93 vs 944 msec ± 120; P = .01). Estimated T1 of normal vessel wall and muscle were 1195 msec ± 136 and 1117 msec ± 153, respectively. Conclusion High-spatial-resolution (0.8 mm isotropic) time-efficient (5 minutes) vessel wall T1 mapping is achieved by using the GOAL-SNAP sequence. This sequence may yield more quantitative reproducible biomarkers with which to characterize IPH and monitor its progression. © RSNA, 2017.

Large coverage black-bright blood interleaved imaging sequence (LaBBI) for 3D dynamic contrast-enhanced MRI of vessel wall.

PURPOSE: To propose a large coverage black-bright blood interleaved imaging sequence (LaBBI) for 3D dynamic contrast-enhanced MRI (DCE-MRI) of the vessel wall. METHODS: LaBBI consists of a 3D black-blood stack-of-stars golden angle radial acquisition with high spatial resolution for vessel wall imaging and a 2D bright-blood Cartesian acquisition with high temporal resolution for arterial input function estimation. The two acquisitions were performed in an interleaved fashion within a single scan. Simulations, phantom experiments, and in vivo tests in three patients were performed to investigate the feasibility and performance of the proposed LaBBI. RESULTS: In simulation tests, the estimated Ktrans and vp by LaBBI were more accurate than conventional bright-blood DCE-MRI with lower root mean square error in all the tested conditions. In phantom test, no signal interference was found on the 2D scan in LaBBI. Pharmacokinetic analysis of the patients' data acquired by LaBBI showed that Ktrans was higher in fibrous tissue (0.0717 ± 0.0279 min-1 ), while lower in necrotic core (0.0206 ± 0.0040 min-1 ) and intraplaque hemorrhage (0.0078 ± 0.0007 min-1 ), compared with normal vessel wall (0.0273 ± 0.0052 min-1 ). CONCLUSION: The proposed LaBBI sequence, with high spatial and temporal resolution, and large coverage blood suppression, was promising to probe the perfusion properties of vessel wall lesions. Magn Reson Med 79:1334-1344, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Evaluation of carotid atherosclerotic plaque surface characteristics utilizing simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) technique.

PURPOSE: To evaluate the feasibility of the Simultaneous Noncontrast Angiography and intraPlaque hemorrhage (SNAP) technique in identification of carotid plaque surface characteristics compared with the conventional multicontrast vessel wall imaging protocol. MATERIALS AND METHODS: Thirty symptomatic patients with carotid plaque were recruited and underwent carotid artery magnetic resonance imaging (MRI) (3.0T) using a conventional multicontrast protocol and SNAP sequence. As an intrinsic multicontrast sequence, SNAP could generate a gray blood reference (Ref) image set, a black blood corrected real (CR) image set, and a bright blood MR angiography (MRA) image set. A bright blood SNAP Ref2 image was implemented by combining Ref and MRA images for facilitating plaque surface characteristics evaluation. The presence/absence of calcification (CA), juxtaluminal calcification (JCA), and ulceration was assessed. The agreement between SNAP and multicontrast vessel wall protocol in identifying CA, JCA, and ulceration was analyzed using Cohen's kappa analysis. The interreader and intrareader reproducibility of SNAP imaging in identifying plaque surface characteristics was also assessed. RESULTS: Good to excellent agreement was found between SNAP and conventional multicontrast protocol in identifying CA (κ = 0.74, 95% confidence interval [CI]: 0.54-0.93), JCA (κ = 0.81, 95% CI: 0.66-0.97), and ulceration (κ = 0.82, 95% CI: 0.65-0.99). In addition, excellent intrareader and interreader reproducibility was found for SNAP imaging in identification of CA, JCA, and ulceration. CONCLUSION: SNAP imaging showed excellent agreement with multicontrast imaging and high reproducibility in identification of both JCA and ulceration, suggesting that SNAP imaging may be a time-efficient, alternative tool in identification of plaque surface characteristics in carotid arteries. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:634-639.

Fast simultaneous noncontrast angiography and intraplaque hemorrhage (fSNAP) sequence for carotid artery imaging.

PURPOSE: To propose a fast simultaneous noncontrast angiography and intraplaque hemorrhage (fSNAP) sequence for carotid artery imaging. METHODS: The proposed fSNAP sequence uses a low-resolution reference acquisition for phase-sensitive reconstruction to speed up the scan, and an inversion recovery acquisition with arbitrary k-space filling order to generate similar contrast to conventional SNAP. Four healthy volunteers and eight patients were recruited to test the performance of fSNAP in vivo. The lumen area quantification, muscle-blood CNR, IPH-blood CNR, lumen SNR, and standard deviation and intraplaque hemorrhage (IPH) detection accuracy were compared between fSNAP and SNAP. RESULTS: By using a low-resolution reference acquisition with 1/4 matrix size of the full-resolution reference scan, the scan time of fSNAP was 37.5% less than that of SNAP. A high agreement of lumen area measurement (ICC = 0.97, 95% CI: 0.96-0.99) and IPH detection (Kappa = 1) were found between fSNAP and SNAP. Also, no significant difference was found for muscle-blood CNR (P = 0.25), IPH-blood CNR (P = 0.35), lumen SNR (P = 0.60), and standard deviation (P = 0.46) between the two techniques. CONCLUSION: The feasibility of fSNAP was validated. fSNAP can improve the imaging efficiency with similar performance to SNAP on carotid artery imaging. Magn Reson Med 77:753-758, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Accelerated phase contrast flow imaging with direct complex difference reconstruction.

PURPOSE: To propose and evaluate a new model-based reconstruction method for highly accelerated phase-contrast magnetic resonance imaging (PC-MRI) with sparse sampling. THEORY AND METHODS: This work presents a new constrained reconstruction method based on low-rank and sparsity constraints to accelerate PC-MRI. More specifically, we formulate the image reconstruction problem into separate reconstructions of flow-reference image sequence and complex differences. We then utilize the joint partial separability and sparsity constraints to enable high quality reconstruction from highly undersampled (k,t)-space data. We further integrate the proposed method with ESPIRiT based parallel imaging model to effectively handle multichannel acquisition. RESULTS: The proposed method was evaluated with in vivo data acquired from both 2D and 3D PC flow imaging experiments, and compared with several state-of-the-art methods. Experimental results demonstrate that the proposed method leads to more accurate velocity reconstruction from highly undersampled (k,t)-space data, and particularly superior capability of capturing the peak velocity of blood flow. In terms of flow visualization, blood flow patterns obtained from the proposed reconstruction also exhibit better agreement with those obtained from the fully sampled reference. CONCLUSION: The proposed method achieves improved accuracy over several state-of-the-art methods for velocity reconstruction with highly accelerated (k,t)-space data. Magn Reson Med 77:1036-1048, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Association between proximal internal carotid artery steno-occlusive disease and diffuse wall thickening in its petrous segment: a magnetic resonance vessel wall imaging study.

PURPOSE: Significant stenosis or occlusion in carotid arteries may lead to diffuse wall thickening (DWT) in the arterial wall of downstream. This study aimed to investigate the correlation between proximal internal carotid artery (ICA) steno-occlusive disease and DWT in ipsilateral petrous ICA. METHODS: Symptomatic patients with atherosclerotic stenosis (>0%) in proximal ICA were recruited and underwent carotid MR vessel wall imaging. The 3D motion sensitized-driven equilibrium prepared rapid gradient-echo (3D-MERGE) was acquired for characterizing the wall thickness and longitudinal extent of the lesions in petrous ICA and the distance from proximal lesion to the petrous ICA. The stenosis degree in proximal ICA was measured on the time-of-flight (TOF) images. RESULTS: In total, 166 carotid arteries from 125 patients (mean age 61.0 ± 10.5 years, 99 males) were eligible for final analysis and 64 showed DWT in petrous ICAs. The prevalence of severe DWT in petrous ICA was 1.4%, 5.3%, 5.9%, and 80.4% in ipsilateral proximal ICAs with stenosis category of 1%-49%, 50%-69%, 70%-99%, and total occlusion, respectively. Proximal ICA stenosis was significantly correlated with the wall thickness in petrous ICA (r = 0.767, P < 0.001). Logistic regression analysis showed that proximal ICA stenosis was independently associated with DWT in ipsilateral petrous ICA (odds ratio (OR) = 2.459, 95% confidence interval (CI) 1.896-3.189, P < 0.001]. CONCLUSION: Proximal ICA steno-occlusive disease is independently associated with DWT in ipsilateral petrous ICA.

STEP: Self-supporting tailored k-space estimation for parallel imaging reconstruction.

PURPOSE: A new subspace-based iterative reconstruction method, termed Self-supporting Tailored k-space Estimation for Parallel imaging reconstruction (STEP), is presented and evaluated in comparison to the existing autocalibrating method SPIRiT and calibrationless method SAKE. THEORY AND METHODS: In STEP, two tailored schemes including k-space partition and basis selection are proposed to promote spatially variant signal subspace and incorporated into a self-supporting structured low rank model to enforce properties of locality, sparsity, and rank deficiency, which can be formulated into a constrained optimization problem and solved by an iterative algorithm. Simulated and in vivo datasets were used to investigate the performance of STEP in terms of overall image quality and detail structure preservation. RESULTS: The advantage of STEP on image quality is demonstrated by retrospectively undersampled multichannel Cartesian data with various patterns. Compared with SPIRiT and SAKE, STEP can provide more accurate reconstruction images with less residual aliasing artifacts and reduced noise amplification in simulation and in vivo experiments. In addition, STEP has the capability of combining compressed sensing with arbitrary sampling trajectory. CONCLUSION: Using k-space partition and basis selection can further improve the performance of parallel imaging reconstruction with or without calibration signals.

Joint blood and cerebrospinal fluid suppression for intracranial vessel wall MRI.

PURPOSE: To develop and evaluate a joint blood and cerebrospinal fluid (CSF) suppression technique for improved intracranial vessel wall MR imaging. METHODS: The Delay Alternating with Nutation for Tailored Excitation (DANTE) prepulse was specifically optimized for CSF suppression to improve vessel wall and CSF contrast. It was evaluated on six patients and three healthy volunteers. CSF suppression efficiency, lumen signal to noise ratio, and wall-lumen contrast to noise ratio were compared between images with and without DANTE in major intercranial artery segments. Contrast changes in tissues were also compared with evaluate the technique's compatibility with multicontrast imaging techniques. RESULTS: The optimized DANTE images significantly improved intracranial vessel wall characterization on all images. Quantitatively, CSF to wall contrast improved by 28% (DANTE-VISTA 1.354 ± 0.216 versus VISTA 1.057 ± 0.13; P < 0.001). DANTE also significantly improved wall-lumen (10.55 ± 3.79 versus 9.34 ± 3.54; P < 0.001) and wall-CSF (4.62 ± 3.19 versus 0.78 ± 2.30; P < 0.001) contrast-to-noise ratios. DANTE prepared images were also found to make only minimal impact on static tissue contrast. CONCLUSION: DANTE prepared MR imaging can significantly improve contrast between the vessel wall and cerebral spinal fluid in major intracranial arteries, holding a good potential to be combined with multicontrast protocol for intracranial wall imaging.

Co-existing intracranial and extracranial carotid artery atherosclerotic plaques and recurrent stroke risk: a three-dimensional multicontrast cardiovascular magnetic resonance study.

BACKGROUND: As a systemic disease, atherosclerosis commonly affects intracranial and extracranial carotid arteries simultaneously which is defined as co-existing plaques. Previous studies demonstrated that co-existing atherosclerotic diseases are significantly associated with ischemic cerebrovascular events. The aim of this study was to investigate the characteristics of co-existing intracranial and extracranial carotid atherosclerotic plaques and their relationships with recurrent stroke by using 3D multi-contrast magnetic resonance (MR) vessel wall imaging. METHODS: Patients with recent cerebrovascular symptoms in anterior circulation and at least one carotid plaque were recruited. All patients underwent cardiovascular magnetic resonance (CMR) for brain and intracranial and extracranial arteries. Presence/absence of atherosclerotic plaque at each arterial segment was identified. The maximum wall thickness (Max WT), length, stenosis of each plaque was measured. The presence/absence of calcification, lipid-rich necrotic core (LRNC), and intraplaque hemorrhage (IPH) was assessed. Cerebral old and acute infarcts in anterior circulation were evaluated. RESULTS: Fifty-eight patients (mean age: 58.0 ± 8.5 years old, 34 males) were recruited. Of the 58 patients, co-existing intracranial and extracranial carotid artery plaques were found in 45 patients (77.6%), of which 7 (15.6%) had first time acute stroke and 26 (57.8%) had recurrent stroke. For these 33 patients with stroke, the number of intracranial plaques (OR = 11.26; 95% CI, 1.27-100; p = 0.030) and co-existing intracranial and extracranial carotid artery plaques (OR = 2.42; 95% CI, 1.04-5.64; p = 0.040) was significantly associated with recurrent stroke. After adjusting for traditional risk factors, the number of co-existing plaques was still significantly correlated with recurrent stroke (OR = 3.31; 95% CI, 1.09-10.08; p = 0.035). No correlations were found between recurrent stroke and Max WT, length, stenosis, and compositions of plaques. CONCLUSIONS: Co-existing intracranial and extracranial carotid artery plaques are prevalent in symptomatic patients and the number of co-existing plaques is independently associated with the risk of recurrent stroke.

Homologous HOmologous Black-Bright-blood and flexible Interleaved imaging sequence (HOBBI) for dynamic contrast-enhanced MRI of the vessel wall.

PURPOSE: To present a HOmologous Black-Bright-blood and flexible Interleaved imaging (HOBBI) sequence for dynamic contrast-enhanced magnetic resonance imaging (MRI) of the vessel wall. THEORY AND METHODS: A HOBBI sequence is proposed to acquire high-spatial-resolution black-blood and high-temporal-resolution bright-blood dynamic contrast-enhanced images in an interleaved fashion. Black-blood imaging allows for thin vessel wall evaluation, whereas bright-blood imaging obtains the arterial input function accurately. A simulation was performed to assess the accuracy of the pharmacokinetic parameters [transfer constant (K(trans) ) and fractional plasma volume (vp )] generated from HOBBI. In vivo evaluation was also used to validate HOBBI in an animal model of aortic atherosclerosis. RESULTS: In the simulation test, the estimated K(trans) and vp measured by HOBBI were more accurate than those from black-blood dynamic contrast-enhanced-MRI. In the animal model testing, K(trans) and vp also demonstrated good interscan reproducibility (K(trans) : ICC = 0.77, vp : ICC = 0.72, respectively). Additionally, K(trans) showed a significant increase from 1 month (0.026 ± 0.013 min(-1) ) to 2 months (0.069 ± 0.018 min(-1) ) in animal model plaque progression after balloon injury. CONCLUSION: The proposed HOBBI sequence was demonstrated to be feasible and accurate in estimating the pharmacokinetic parameters of the atherosclerotic vessel wall, and has potential to become an early screening tool for atherosclerosis disease.

Evaluation of 3D multi-contrast joint intra- and extracranial vessel wall cardiovascular magnetic resonance.

BACKGROUND: Multi-contrast vessel wall cardiovascular magnetic resonance (CMR) has demonstrated its capability for atherosclerotic plaque morphology measurement and component characterization in different vasculatures. However, limited coverage and partial volume effect with conventional two-dimensional (2D) techniques might cause lesion underestimation. The aim of this work is to evaluate the performance in a) blood suppression and b) vessel wall delineation of three-dimensional (3D) multi-contrast joint intra- and extracranial vessel wall imaging at 3T. METHODS: Three multi-contrast 3D black blood (BB) sequences with T1, T2 and heavy T1 weighting and a custom designed 36-channel neurovascular coil covering the entire intra- and extracranial vasculature have been used and investigated in this study. Two healthy subjects were recruited for sequence parameter optimization and twenty-five patients were consecutively scanned for image quality and blood suppression assessment. Qualitative image scores of vessel wall delineation as well as quantitative Signal-to-Noise Ratio (SNR) and Contrast-to-Noise Ratio (CNR) were evaluated at five typical locations ranging from common carotid arteries to middle cerebral arteries. RESULTS: The 3D multi-contrast images acquired within 15mins allowed the vessel wall visualization with 0.8 mm isotropic spatial resolution covering intra- and extracranial segments. Quantitative wall and lumen SNR measurements for each sequence showed effective blood suppression at all selected locations (P < 0.0001). Although the wall-lumen CNR varied across measured locations, each sequence provided good or adequate image quality in both intra- and extracranial segments. CONCLUSIONS: The proposed 3D multi-contrast vessel wall technique provides isotropic resolution and time efficient solution for joint intra- and extracranial vessel wall CMR.