Quantitative transport mapping (QTM) of the kidney with an approximate microvascular network.

PURPOSE: Proof-of-concept study of mapping renal blood flow vector field according to the inverse solution to a mass transport model of time resolved tracer-labeled MRI data. THEORY AND METHODS: To determine tissue perfusion according to the underlying physics of spatiotemporal tracer concentration variation, the mass transport equation is integrated over a voxel with an approximate microvascular network for fitting time-resolved tracer imaging data. The inverse solution to the voxelized transport equation provides the blood flow vector field, which is referred to as quantitative transport mapping (QTM). A numerical microvascular network modeling the kidney with computational fluid dynamics reference was used to verify the accuracy of QTM and the current Kety's method that uses a global arterial input function. Multiple post-label delay arterial spin labeling (ASL) of the kidney on seven subjects was used to assess QTM in vivo feasibility. RESULTS: Against the ground truth in the numerical model, the error in flow estimated by QTM (18.6%) was smaller than that in Kety's method (45.7%, 2.5-fold reduction). The in vivo kidney perfusion quantification by QTM (cortex: 443 ± 58 mL/100 g/min and medulla: 190 ± 90 mL/100 g/min) was in the range of that by Kety's method (482 ± 51 mL/100 g/min in the cortex and 242 ± 73 mL/100 g/min in the medulla), and QTM provided better flow homogeneity in the cortex region. CONCLUSIONS: QTM flow velocity mapping is feasible from multi-delay ASL MRI data based on inverting the transport equation. In a numerical simulation, QTM with deconvolution in space and time provided more accurate perfusion quantification than Kety's method with deconvolution in time only.

Non-invasive measurement of choroid plexus apparent blood flow with arterial spin labeling.

BACKGROUND: The choroid plexus is a major contributor to the generation of cerebrospinal fluid (CSF) and the maintenance of its electrolyte and metabolite balance. Here, we sought to characterize the blood flow dynamics of the choroid plexus using arterial spin labeling (ASL) MRI to establish ASL as a non-invasive tool for choroid plexus function and disease studies. METHODS: Seven healthy volunteers were imaged on a 3T MR scanner. ASL images were acquired with 12 labeling durations and post labeling delays. Regions of the choroid plexus were manually segmented on high-resolution T1 weighted images. Choroid plexus perfusion was characterized with a dynamic ASL perfusion model. Cerebral gray matter perfusion was also quantified for comparison. RESULTS: Kinetics of the ASL signal were clearly different in the choroid plexus than in gray matter. The choroid plexus has a significantly longer T1 than the gray matter (2.33 ± 0.30 s vs. 1.85 ± 0.10 s, p < 0.02). The arterial transit time was 1.24 ± 0.20 s at the choroid plexus. The apparent blood flow to the choroid plexus was measured to be 39.5 ± 10.1 ml/100 g/min and 0.80 ± 0.31 ml/min integrated over the posterior lateral ventricles in both hemispheres. Correction with the choroid plexus weight yielded a blood flow of 80 ml/100 g/min. CONCLUSIONS: Our findings suggest that ASL can provide a clinically feasible option to quantify the dynamic characteristics of choroid plexus blood flow. It also provides useful reference values of the choroid plexus perfusion. The long T1 of the choroid plexus may suggest the transport of water from arterial blood to the CSF, potentially providing a method to quantify CSF generation.

Identifying cardiovascular risk factors that impact cerebrovascular reactivity: An ASL MRI study.

BACKGROUND: To maintain cerebral blood flow (CBF), cerebral blood vessels dilate and contract in response to blood supply through cerebrovascular reactivity (CR). PURPOSE: Cardiovascular (CV) disease is associated with increased stroke risk, but which risk factors specifically impact CR is unknown. STUDY TYPE: Prospective longitudinal. SUBJECTS: Fifty-three subjects undergoing carotid endarterectomy or stenting. FIELD STRENGTH/SEQUENCE: 3T, 3D pseudo-continuous arterial spin labeling (PCASL) ASL, and T1 3D fast spoiled gradient echo (FSPGR). ASSESSMENT: We evaluated group differences in CBF changes for multiple cardiovascular risk factors in patients undergoing carotid revascularization surgery. STATISTICAL TESTS: PRE (baseline), POST (48-hour postop), and 6MO (6 months postop) whole-brain CBF measurements, as 129 CBF maps from 53 subjects were modeled as within-subject analysis of variance (ANOVA). To identify CV risk factors associated with CBF change, the CBF change from PRE to POST, POST to 6MO, and PRE to 6MO were modeled as multiple linear regression with each CV risk factor as an independent variable. Statistical models were performed controlling for age on a voxel-by-voxel basis using SPM8. Significant clusters were reported if familywise error (FWE)-corrected cluster-level was P < 0.05, while the voxel-level significance threshold was set for P < 0.001. RESULTS: The entire group showed significant (cluster-level P < 0.001) CBF increase from PRE to POST, decrease from POST to 6MO, and no significant difference (all voxels with P > 0.001) from PRE to 6MO. Of multiple CV risk factors evaluated, only elevated systolic blood pressure (SBP, P = 0.001), chronic renal insufficiency (CRI, P = 0.026), and history of prior stroke (CVA, P < 0.001) predicted lower increases in CBF PRE to POST. Over POST to 6MO, obesity predicted lower (P > 0.001) and cholesterol greater CBF decrease (P > 0.001). DATA CONCLUSION: The CV risk factors of higher SBP, CRI, CVA, BMI, and cholesterol may indicate altered CR, and may warrant different stroke risk mitigation and special consideration for CBF change evaluation. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2020;51:734-747.

Human umbilical cord mesenchymal stem cells pretreated with Angiotensin-II attenuate pancreas injury of rats with severe acute pancreatitis.

Mesenchymal stem cells (MSCs) pretreatment is an effective route for improving cell-based therapy of endothelial cell survival, vascular stabilization, and angiogenesis. We hypothesized that the application of human umbilical cord-MSCs (hUC-MSCs) pretreated with angiotensin-II (Ang-II) might be a potential therapeutic approach for severe acute pancreatitis (SAP). Therefore, the effect of Ang-II pretreated hUC-MSCs on SAP was investigated in vitro and in vivo. METHODS: In the present study, human umbilical cord-derived MSCs pretreated with or without Ang-II were delivered through the tail vein of rats 12 h after induction of SAP. Pancreatitis severity scores and serum lipase levels, as well as the levels of VEGF and VEGFR2 were evaluated. RESULTS: We found that the administration of Ang-II-MSCs significantly inhibited pancreatic injury, as reflected by reductions of pancreatitis severity scores, serum amylase and serum lipase levels. Furthermore, the reduced apoptotic rate and increased tube formation in human umbilical vein endothelial Cells (HUVEC) were found resulting from the administration of Ang-II-MSC-CM. Moreover, knockdown of VEGFR2 can block the effect of Ang-II-MSC-CM on preventing HUVEC from apoptosis, as well as the capacity of tube formation was also suppressed. In addition, the expression of increased Bcl-2 and alleviated caspase-3 were observed in HUVEC and HUVEC transfectants exposure to Ang-II-MSC-CM. CONCLUSION: Collectively, these results elucidated that the pretreatment of hUC-MSCs with Ang-II improved the outcome of MSC-based therapy for SAP via enhancing angiogenesis and ameliorating endothelial cell dysfunction in a VEGFR2 dependent manner.

Postoperative Delirium and Postoperative Cognitive Dysfunction: Overlap and Divergence.

BACKGROUND: Postoperative delirium and postoperative cognitive dysfunction share risk factors and may co-occur, but their relationship is not well established. The primary goals of this study were to describe the prevalence of postoperative cognitive dysfunction and to investigate its association with in-hospital delirium. The authors hypothesized that delirium would be a significant risk factor for postoperative cognitive dysfunction during follow-up. METHODS: This study used data from an observational study of cognitive outcomes after major noncardiac surgery, the Successful Aging after Elective Surgery study. Postoperative delirium was evaluated each hospital day with confusion assessment method-based interviews supplemented by chart reviews. Postoperative cognitive dysfunction was determined using methods adapted from the International Study of Postoperative Cognitive Dysfunction. Associations between delirium and postoperative cognitive dysfunction were examined at 1, 2, and 6 months. RESULTS: One hundred thirty-four of 560 participants (24%) developed delirium during hospitalization. Slightly fewer than half (47%, 256 of 548) met the International Study of Postoperative Cognitive Dysfunction-defined threshold for postoperative cognitive dysfunction at 1 month, but this proportion decreased at 2 months (23%, 123 of 536) and 6 months (16%, 85 of 528). At each follow-up, the level of agreement between delirium and postoperative cognitive dysfunction was poor (kappa less than .08) and correlations were small (r less than .16). The relative risk of postoperative cognitive dysfunction was significantly elevated for patients with a history of postoperative delirium at 1 month (relative risk = 1.34; 95% CI, 1.07-1.67), but not 2 months (relative risk = 1.08; 95% CI, 0.72-1.64), or 6 months (relative risk = 1.21; 95% CI, 0.71-2.09). CONCLUSIONS: Delirium significantly increased the risk of postoperative cognitive dysfunction in the first postoperative month; this relationship did not hold in longer-term follow-up. At each evaluation, postoperative cognitive dysfunction was more common among patients without delirium. Postoperative delirium and postoperative cognitive dysfunction may be distinct manifestations of perioperative neurocognitive deficits.

Effect of lncRNA ANRIL silencing on anoikis and cell cycle in human glioma via microRNA-203a.

BACKGROUND: Glioma is a deadly nervous system tumor with a poor prognosis. Although there have been many efforts to overcome glioma, the molecular mechanism of its pathogenesis remains unclear. METHODS: We used human glioma U251 cells silenced for the oncogenic lncRNA ANRIL or overexpressing the anti-oncogene miR-203a to examine the role of lncRNA ANRIL silencing on anoikis and cell cycle arrest by flow cytometry. Meanwhile, the activity of caspase-3/8/9 was measured by fluorometric assay, the expression of tumor-related genes and activity of AKT signaling pathway was measured by Western blotting, real-time PCR, and dual luciferase reporter gene assay. RESULTS: lncRNA ANRIL was positively correlated with glioma grade and negatively correlated with miR-203a. lncRNA ANRIL silencing could induce anoikis and cell cycle arrest in G0/G1 phase, while regulating the activity of caspase-3/8/9 and the AKT signaling pathway, and the expression of tumor-related genes in the U251 cell line. miR-203a mimics could partially reverse these functions. CONCLUSION: We consider that lncRNA ANRIL is a potential therapeutic and diagnostic target for glioma, and miR-203a plays an important role in the biological function of lncRNA ANRIL in glioma.

Longitudinal diffusion changes following postoperative delirium in older people without dementia.

OBJECTIVE: To investigate the effect of postoperative delirium on longitudinal brain microstructural changes, as measured by diffusion tensor imaging. METHODS: We studied a subset of the larger Successful Aging after Elective Surgery (SAGES) study cohort of older adults (≥70 years) without dementia undergoing elective surgery: 113 participants who had diffusion tensor imaging before and 1 year after surgery. Postoperative delirium severity and occurrence were assessed during the hospital stay using the Confusion Assessment Method and a validated chart review method. We investigated the association of delirium severity and occurrence with longitudinal diffusion changes across 1 year, adjusting for age, sex, vascular comorbidity, and baseline cognitive performance. We also assessed the association between changes in diffusion and cognitive performance across the 1-year follow-up period, adjusting for age, sex, education, and baseline cognitive performance. RESULTS: Postoperative delirium occurred in 25 participants (22%). Delirium severity and occurrence were associated with longitudinal diffusion changes in the periventricular, frontal, and temporal white matter. Diffusion changes were also associated with changes in cognitive performance across 1 year, although the cognitive changes did not show significant association with delirium severity or occurrence. CONCLUSIONS: Our study raises the possibility that delirium has an effect on the development of brain microstructural abnormalities, which may reflect brain changes underlying cognitive trajectories. Future studies are warranted to clarify whether delirium is the driving factor of the observed changes or rather a correlate of a vulnerable brain that is at high risk for neurodegenerative processes.

Using Anatomic Magnetic Resonance Image Information to Enhance Visualization and Interpretation of Functional Images: A Comparison of Methods Applied to Clinical Arterial Spin Labeling Images.

Functional imaging provides hemodynamic and metabolic information and is increasingly being incorporated into clinical diagnostic and research studies. Typically functional images have reduced signal-to-noise ratio and spatial resolution compared to other non-functional cross sectional images obtained as part of a routine clinical protocol. We hypothesized that enhancing visualization and interpretation of functional images with anatomic information could provide preferable quality and superior diagnostic value. In this work, we implemented five methods (frequency addition, frequency multiplication, wavelet transform, nonsubsampled contourlet transform and intensity-hue-saturation) and a newly proposed ShArpening by Local Similarity with Anatomic images (SALSA) method to enhance the visualization of functional images, while preserving the original functional contrast and quantitative signal intensity characteristics over larger spatial scales. Arterial spin labeling blood flow MR images of the brain were visualization enhanced using anatomic images with multiple contrasts. The algorithms were validated on a numerical phantom and their performance on images of brain tumor patients were assessed by quantitative metrics and neuroradiologist subjective ratings. The frequency multiplication method had the lowest residual error for preserving the original functional image contrast at larger spatial scales (55%-98% of the other methods with simulated data and 64%-86% with experimental data). It was also significantly more highly graded by the radiologists (p<0.005 for clear brain anatomy around the tumor). Compared to other methods, the SALSA provided 11%-133% higher similarity with ground truth images in the simulation and showed just slightly lower neuroradiologist grading score. Most of these monochrome methods do not require any prior knowledge about the functional and anatomic image characteristics, except the acquired resolution. Hence, automatic implementation on clinical images should be readily feasible.

Cerebral blood flow MRI in the nondemented elderly is not predictive of post-operative delirium but is correlated with cognitive performance.

Three-dimensional Arterial Spin Labeling (ASL) MRI was performed before surgery in a cohort of 146 prospectively enrolled subjects ≥ 70 years old scheduled to undergo elective surgery. We investigated the prospective association between ASL-derived measures of cerebral blood flow (CBF) before surgery with postoperative delirium incidence and severity using whole-brain and globally normalized voxel-wise analysis. We also investigated the cross-sectional association of CBF with patients' baseline performance on specific neuropsychological tests, and with a composite general cognitive performance measure (GCP). Out of 146 subjects, 32 (22%) developed delirium. We found no significant association between global and voxel-wise CBF with delirium incidence or severity. We found the most significant positive associations between CBF of the posterior cingulate and precuneus and the Hopkins Verbal Learning Test - Revised total score, Visual Search and Attention Test (VSAT) score and the GCP composite. VSAT score was also strongly associated with right parietal lobe CBF. ASL can be employed in a large, well-characterized older cohort to examine associations between CBF and age-related cognitive performance. Although ASL CBF measures in regions previously associated with preclinical Alzheimer's Disease were correlated with cognition, they were not found to be indicators of baseline pathology that may increase risk for delirium.

Neural substrates of vulnerability to postsurgical delirium as revealed by presurgical diffusion MRI.

Despite the significant impact of postoperative delirium on surgical outcomes and the long-term prognosis of older patients, its neural basis has not yet been clarified. In this study we investigated the impact of premorbid brain microstructural integrity, as measured by diffusion tensor imaging before surgery, on postoperative delirium incidence and severity, as well as the relationship among presurgical cognitive performance, diffusion tensor imaging abnormalities and postoperative delirium. Presurgical diffusion tensor imaging scans of 136 older (≥70 years), dementia-free subjects from the prospective Successful Aging after Elective Surgery study were analysed blind to the clinical data and delirium status. Primary outcomes were postoperative delirium incidence and severity during the hospital stay, as assessed by the Confusion Assessment Method. We measured cognition before surgery using general cognitive performance, a composite score based on a battery of neuropsychological tests. We investigated the association between presurgical diffusion tensor imaging parameters of brain microstructural integrity (i.e. fractional anisotropy, axial, mean and radial diffusivity) with postoperative delirium incidence and severity. Analyses were adjusted for the following potential confounders: age, gender, vascular comorbidity status, and general cognitive performance. Postoperative delirium occurred in 29 of 136 subjects (21%) during hospitalization. Presurgical diffusion tensor imaging abnormalities of the cerebellum, cingulum, corpus callosum, internal capsule, thalamus, basal forebrain, occipital, parietal and temporal lobes, including the hippocampus, were associated with delirium incidence and severity, after controlling for age, gender and vascular comorbidities. After further controlling for general cognitive performance, diffusion tensor imaging abnormalities of the cerebellum, hippocampus, thalamus and basal forebrain still remained associated with delirium incidence and severity. This study raises the intriguing possibility that structural dysconnectivity involving interhemispheric and fronto-thalamo-cerebellar networks, as well as microstructural changes of structures involved in limbic and memory functions predispose to delirium under the stress of surgery. While the diffusion tensor imaging abnormalities observed in the corpus callosum, cingulum, and temporal lobe likely constitute the neural substrate for the association between premorbid cognition, as measured by general cognitive performance, and postoperative delirium, the microstructural changes observed in the cerebellum, hippocampus, thalamus and basal forebrain seem to constitute a separate phenomenon that predisposes to postsurgical delirium independent of presurgical cognitive status.

Volumetric Arterial Spin-labeled Perfusion Imaging of the Kidneys with a Three-dimensional Fast Spin Echo Acquisition.

RATIONALE AND OBJECTIVES: Renal perfusion measurements using noninvasive arterial spin-labeled (ASL) magnetic resonance imaging techniques are gaining interest. Currently, focus has been on perfusion in the context of renal transplant. Our objectives were to explore the use of ASL in patients with renal cancer, and to evaluate three-dimensional (3D) fast spin echo (FSE) acquisition, a robust volumetric imaging method for abdominal applications. We evaluate 3D ASL perfusion magnetic resonance imaging in the kidneys compared to two-dimensional (2D) ASL in patients and healthy subjects. MATERIALS AND METHODS: Isotropic resolution (2.6 × 2.6 × 2.8 mm(3)) 3D ASL using segmented FSE was compared to 2D single-shot FSE. ASL used pseudo-continuous labeling, suppression of background signal, and synchronized breathing. Quantitative perfusion values and signal-to-noise ratio (SNR) were compared between 3D and 2D ASL in four healthy volunteers and semiquantitative assessments were made by four radiologists in four patients with known renal masses (primary renal cell carcinoma). RESULTS: Renal cortex perfusion in healthy subjects was 284 ± 21 mL/100 g/min, with test-retest repeatability of 8.8%. No significant differences were found between the quantitative perfusion value and SNR in volunteers between 3D ASL and 2D ASL, or in 3D ASL with synchronized or free breathing. In patients, semiquantitative assessment by radiologists showed no significant difference in image quality between 2D ASL and 3D ASL. In one case, 2D ASL missed a high perfusion focus in a mass that was seen by 3D ASL. CONCLUSIONS: 3D ASL renal perfusion imaging provides isotropic-resolution images, with comparable quantitative perfusion values and image SNR in similar imaging time to single-slice 2D ASL.

Continuous flow-driven inversion for arterial spin labeling using pulsed radio frequency and gradient fields.

Continuous labeling by flow-driven adiabatic inversion is advantageous for arterial spin labeling (ASL) perfusion studies, but details of the implementation, including inefficiency, magnetization transfer, and limited support for continuous-mode operation on clinical scanners, have restricted the benefits of this approach. Here a new approach to continuous labeling that employs rapidly repeated gradient and radio frequency (RF) pulses to achieve continuous labeling with high efficiency is characterized. The theoretical underpinnings, numerical simulations, and in vivo implementation of this pulsed continuous ASL (PCASL) method are described. In vivo PCASL labeling efficiency of 96% relative to continuous labeling with comparable labeling parameters far exceeded the 33% duty cycle of the PCASL RF pulses. Imaging at 3T with body coil transmission was readily achieved. This technique should help to realize the benefits of continuous labeling in clinical imagers.