Reproducibility of diffusion tensor imaging-derived parameters: implications for the streptozotocin-induced type 1 diabetic rats.

OBJECTIVE: Diffusion tensor imaging (DTI) is a useful approach for studying neuronal integrity in animals. However, the test-retest reproducibility of DTI techniques in animals has not been discussed. Therefore, the first part of this work was to systematically elucidate the reliability of DTI-derived parameters in an animal study. Subsequently, we applied the DTI approach to an animal model of diabetes in a longitudinal manner. MATERIALS AND METHODS: In Study 1, nine rats underwent two DTI sessions using the same scanner and protocols, with a gap of 4 weeks. The reliability of the DTI-derived parameters was evaluated in terms of sessions and raters. In Study 2, nine rats received a single intraperitoneal injection of 70 mg/kg streptozotocin (STZ) to develop diabetes. Longitudinal DTI scans were used to assess brain alterations before and 4 weeks after STZ administration. RESULTS: In the test-retest evaluation, the inter-scan coefficient of variation (CoV) ranged from 3.04 to 3.73% and 2.12-2.59% for fractional anisotropy (FA) and mean diffusivity (MD), respectively, in different brain regions, suggesting excellent reproducibility. Moreover, rater-dependence had minimal effects on FA and MD quantification, with all inter-rater CoV values less than 4%. Following the onset of diabetes, FA in striatum and cortex were noted to be significantly lower relative to the period where they had not developed diabetes (both P < 0.05). However, when compared to the control group, a significant change in FA caused by diabetes was detected only in the striatum (P < 0.05), but not in the cortex. CONCLUSION: These results demonstrate good inter-rater and inter-scan reliability of DTI in animal studies, and the longitudinal setting has a beneficial effect on detecting small changes in the brain due to diseases.

New classification for bone type at dental implant sites: a dental computed tomography study.

OBJECTIVE: This study proposed a new classification method of bone quantity and quality at the dental implant site using cone-beam computed tomography (CBCT) image analysis, classifying cortical and cancellous bones separately and using CBCT for quantitative analysis. METHODS: Preoperative CBCT images were obtained from 128 implant patients (315 sites). First, measure the crestal cortical bone thickness (in mm) and the cancellous bone density [in grayscale values (GV) and bone mineral density (g/cm3)] at the implant sites. The new classification for bone quality at the implant site proposed in this study is a "nine-square division" bone classification system, where the cortical bone thickness is classified into A: > 1.1 mm, B:0.7-1.1 mm, and C: < 0.7 mm, and the cancellous bone density is classified into 1: > 600 GV (= 420 g/cm3), 2:300-600 GV (= 160 g/cm3-420 g/cm3), and 3: < 300 GV (= 160 g/cm3). RESULTS: The results of the nine bone type proportions based on the new jawbone classification were as follows: A1 (8.57%,27/315), A2 (13.02%), A3 (4.13%), B1 (17.78%), B2 (20.63%), B3 (8.57%) C1 (4.44%), C2 (14.29%), and C3 (8.57%). CONCLUSIONS: The proposed classification can complement the parts overlooked in previous bone classification methods (bone types A3 and C1). TRIAL REGISTRATION: The retrospective registration of this study was approved by the Institutional Review Board of China Medical University Hospital, No. CMUH 108-REC2-181.

Cerebral hemodynamic response to caffeine: effect of dietary caffeine consumption.

Caffeine has a significant effect on cerebrovascular systems, and the dual action of caffeine on both neural and vascular responses leads to concerns for the interpretation of blood oxygenation level-dependent (BOLD) functional MRI. However, potential differences in the brain response to caffeine with regard to consumption habits have not been fully elucidated, as BOLD responses may vary with the dietary caffeine consumption history. The main aim of this study was to characterize the acute effect of caffeine on cerebral hemodynamic responses in participants with different patterns of caffeine consumption habits. Fifteen non-habitual and 11 habitual volunteers were included in this study. The cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to the breath-hold challenge were measured before and after 200 mg caffeine administration. The non-habitual individuals exhibited a pattern of progressive reduction in CBF with time. The CVR was diminished in the caffeinated condition (P < 0.05). In the habitual group, the pattern of CBF decrease was smaller and homogeneous across the brain, and reached steady state rapidly. The CVR was not affected in the presence of caffeine (P > 0.05). Our results demonstrated that the cerebral hemodynamic response to caffeine was subject to the habitual consumption patterns of the participants. The compromised CVR following caffeine administration in the non-habitual group may partially explain the suppressed BOLD response to a visual stimulation in low-caffeine-level users.

Differences in brain activity between normal and diabetic rats under isoflurane anesthesia: a resting-state functional MRI study.

BACKGROUND: Altered neural activity based on the fractional amplitude of low-frequency fluctuations (fALFF) has been reported in patients with diabetes. However, whether fALFF can differentiate healthy controls from diabetic animals under anesthesia remains unclear. The study aimed to elucidate the changes in fALFF in a rat model of diabetes under isoflurane anesthesia. METHODS: The first group of rats (n = 5) received a single intraperitoneal injection of 70 mg/kg streptozotocin (STZ) to cause the development of diabetes. The second group of rats (n = 7) received a single intraperitoneal injection of the same volume of solvent. Resting-state functional magnetic resonance imaging was used to assess brain activity at 4 weeks after STZ or solvent administration. RESULTS: Compared to the healthy control animals, rats with diabetes showed significantly decreased fALFF in various brain regions, including the cingulate cortex, somatosensory cortex, insula, and striatum (all P < 0.05). The decreased fALFF suggests the aberrant neural activities in the diabetic rats. No regions were detected in which the control group had a lower fALFF than that in the diabetes group. CONCLUSIONS: The results of this study demonstrated that the fALFF could be used to differentiate healthy controls from diabetic animals, providing meaningful information regarding the neurological pathophysiology of diabetes in animal models.

Comparison of 18F-FDG, 18F-Fluoroacetate, and 18F-FEPPA for Imaging Liver Fibrosis in a Bile Duct-Ligated Rat Model.

Developing sensitive diagnostic methods for a longitudinal evaluation of the status of liver fibrosis is a priority. This study is aimed at assessing the significance of longitudinal positron emission tomography (PET) imaging with 18F-labeling tracers for assessing liver fibrosis in a rat model with bile duct ligation (BDL). Twenty-one 6-week-old Sprague-Dawley male rats were used in this study. Longitudinal PET images using [18F]N-2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([18F]FEPPA) (n = 3), [18F]fluoroacetate ([18F]FAc) (n = 3), and 18F-fluoro-2-deoxy-D-glucose ([18F]FDG) (n = 3) were obtained at 0, 1, and 2 weeks after BDL. Biochemical assays, histological assays, immunohistochemical staining assays, and next generation sequencing analyses were also performed at 0 (n = 3), 1 (n = 3), 2 (n = 3), and 3 (n = 3) weeks after BDL, which demonstrated the severe damage in rat livers after BDL. Regarding [18F]FEPPA and [18F]FDG, there was a significantly higher uptake in the liver after BDL (both P < 0.05), which lasted until week 2. However, the uptake of [18F]FAc in the liver was not significantly different before and after BDL (P = 0.28). Collectively, both [18F]FEPPA and [18F]FDG can serve as sensitive probes for detecting the liver fibrosis. However, [18F]FAc is not recommended to diagnose liver fibrosis.

Caffeine enhances BOLD responses to electrical whisker pad stimulation in rats during alpha-chloralose anaesthesia.

By reducing the cerebral blood flow and thereby increasing the resting deoxyhaemoglobin concentration, many human studies have shown that caffeine has a beneficial effect on enhancing the magnitude of blood-oxygenation-level-dependent (BOLD) responses. However, the effect of caffeine on BOLD responses in animals under anaesthesia has not been demonstrated. In this study, we aimed to determine the effect of systemic caffeine administration on BOLD responses in rats under alpha-chloralose. By applying electric whisker pad stimulation to male Sprague-Dawley rats, we performed fMRI measurements before and after the caffeine injection (40 mg/kg, n = 7) or an equivalent volume of saline (n = 6) at 7T. To understand the potential perturbation of animal physiology during stimulation, arterial blood pressure was measured in a separate group of animals (n = 3) outside the scanner. Caffeine significantly decreased baseline BOLD signals (p = .05) due to the increased deoxyhaemoglobin level. Both BOLD responses and t-values in the primary somatosensory cortex were significantly increased (both p < .05). The blood pressure changed insignificantly (p > .05). No significant differences in BOLD responses and t-values were observed in the control condition of saline injection (both p > .05). These findings suggested that, although the cerebral activity was lower under alpha-chloralose anaesthesia, the higher level of deoxygemoglobin at the baseline under the caffeinated condition can benefit the magnitude of BOLD responses in rats. These findings suggest that animal models might serve as potential platforms for further caffeine-related fMRI research studies.

Dynamic contrast-enhanced magnetic resonance imaging in correlation with tongue cancer stages.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) plays a significant role in tumor stage as it can be used to measure tissue perfusion and permeability of tumors. PURPOSE: To investigate the relationships between both quantitative and semi-quantitative variables obtained from DCE-MRI and tongue cancer stages. MATERIAL AND METHODS: Mean values of Ktrans, enhancement ratio (ER), wash-in slope (slope), and the 95th percentile (95%) values of the distribution for Ktrans, ER, and slope values (Ktrans (95%), ER (95%), and slope (95%), respectively) were calculated for 53 patients with tongue cancers (American Joint Committee on Cancer 8th Edition stage group: 10 in stages I and II, 14 in stage III, 21 in stage IVa, and eight in stage IVb as determined by histopathologic assessment). The relationship between tumor staging and each of the six DCE-MRI parameters was assessed separately using ordinal logistic regression. RESULTS: The logistic regression analysis revealed that both mean and 95th percentile values of Ktrans were significantly and positively correlated with tongue cancer stage (P < 0.01). More aggressive tumor stages had larger kinetic parameter. Moreover, the semi-quantitative parameters, such as ER (95%) and slope (95%), may be more significant predictors for evaluating tongue cancer stages than the mean ER and mean slope. CONCLUSION: Both quantitative and semi-quantitative imaging biomarkers are useful for evaluating the stages of tongue cancer, and the indices obtained from DCE-MRI were positively correlated with the tumor stages. These parameters have the potential to non-invasively evaluate the stages of tongue cancer in the clinical setting.

Development of MRI-Detectable Boron-Containing Gold Nanoparticle-Encapsulated Biodegradable Polymeric Matrix for Boron Neutron Capture Therapy (BNCT).

This study aimed to develop a novel magnetic resonance imaging (MRI)-detectable boron (B)-containing nanoassemblies and evaluate their potential for boron neutron capture therapy (BNCT). Starting from the citrate-coated gold nanoparticles (AuNPs) (23.9 ± 10.2 nm), the diameter of poly (D, L-lactide-co-glycolide) AuNPs (PLGA-AuNPs) increased approximately 110 nm after the encapsulation of the PLGA polymer. Among various B drugs, the self-produced B cages had the highest loading efficiency. The average diameter of gadolinium (Gd)- and B-loaded NPs (PLGA-Gd/B-AuNPs) was 160.6 ± 50.6 nm with a B encapsulation efficiency of 28.7 ± 2.3%. In vitro MR images showed that the signal intensity of PLGA-Gd/B-AuNPs in T1-weighted images was proportional to its Gd concentration, and there exists a significantly positive relationship between Gd and B concentrations (R2 = 0.74, p < 0.005). The hyperintensity of either 250 ± 50 mm3 (larger) or 100 ± 50 mm3 (smaller) N87 xenograft was clearly visualized at 1 h after intravenous injection of PLGA-Gd/B-AuNPs. However, PLGA-Gd/B-AuNPs stayed at the periphery of the larger xenograft while located near the center of the smaller one. The tumor-to-muscle ratios of B content, determined by inductively coupled plasma mass spectrometry, in smaller- and larger-sized tumors were 4.17 ± 1.42 and 1.99 ± 0.55, respectively. In summary, we successfully developed theranostic B- and Gd-containing AuNPs for BNCT in this study.

The influence of obesity on cerebral blood flow in young adults using arterial spin labeling MRI.

Obesity causes damage to several organs, including the brain. Recent studies have been focusing on understanding the mechanisms through which obesity affects brain structure and function using neuroimaging techniques. A functional biomarker, such as cerebral blood flow (CBF), is a powerful tool that can be used to explore neural dysfunction. However, there is currently limited information regarding the association between CBF and obesity. The study was conducted to investigate the potential effect of obesity on brain perfusion in a young cohort aged 20-30 years. A total of 21 obese (body mass index (BMI) > 26 kg/m2 ) and 21 lean (BMI < 24 kg/m2 ) right-handed volunteers were included in this study. CBF was acquired using the 2D single post-labeling delay (PLD) arterial spin labeling (ASL) technique on a 3 T MRI scanner. A multiple regression analysis was performed to examine the difference in global and regional gray matter (GM) CBF between the groups. CBF value was assigned as the dependent variable, whereas age, sex, and group (obese or lean) were considered as the independent variables. Results showed that group-related differences in CBF were homogeneous across brain regions, as obese subjects had significantly lower global GM CBF than lean subjects (P < 0.05). In the voxelwise analysis, obese individuals had significantly lower CBF in the left pulvinar of the thalamus and visual association areas, including Brodmann area (BA) 7, BA18, and BA19, than lean subjects. Although the signal-to-noise ratio was slightly compromised for 2D sequences and subject-specific arterial transit time was not estimated due to a single PLD sequence, this study demonstrated alterations in CBF in obese subjects, particularly in regions of the pulvinar of the thalamus and its synchronously related areas such as visual association areas. These results suggest that ASL provides a potential platform for further obesity-related research.

Short- and long-term reproducibility of BOLD signal change induced by breath-holding at 1.5 and 3 T.

Cerebrovascular reactivity (CVR) can give insight into the cerebrovascular function. CVR can be estimated by measuring a blood-oxygen-level-dependent (BOLD) response combined with breath-holding (BH). The reproducibility of this technique has been addressed and existing studies have focused on short-term reproducibility using a 3 T magnetic resonance imaging (MRI) system. However, little is known about the long-term reproducibility of this procedure and the corresponding reproducibility using a 1.5 T MRI system. Here, we systematically examined the short- and long-term reproducibility of BOLD responses to BH across field strengths. Nine subjects participated in three MRI sessions separated by 30 minutes (sessions 1 and 2: short term) and 68-92 days (sessions 1 and 3, long term) at both 1.5 and 3 T MRI. Our findings revealed that significant differences between field strengths were detected in the activated gray matter volume and BOLD signal change (both P < 0.001), with smaller magnitudes at 1.5 T. However, activation patterns were reproducible, independent of the time interval, brain region or field strength. All interscan coefficient of variation values were below the 33% fiducial limit, and the intraclass correlation coefficient values were above 0.4, which is usually considered the acceptability limit in functional studies. These findings suggest that the response of BOLD signal to BH for assessing CVR is reproducible over time at 1.5 and 3 T. This technique can be considered a tool for monitoring longitudinal changes in patients with cerebrovascular diseases, and its use should be encouraged for clinical 1.5 T MRI systems.

The Development of Hyaluronan/Fucoidan-Based Nanoparticles as Macrophages Targeting an Epigallocatechin-3-Gallate Delivery System.

The aim of this study was to develop a macrophage-targeted nanoparticle composed of hyaluronan/fucoidan complexes with polyethylene glycol-gelatin to encapsulate and deliver epigallocatechin-3-gallate (EGCG), a compound that can regulate macrophage activation and pro-inflammatory mediator production. We show that our nanoparticles can successfully bond to macrophages and deliver more EGCG than an EGCG solution treatment, confirming the anti-inflammatory effects of these nanoparticles in lipopolysaccharide-stimulated macrophages. The prepared nanoparticles were established with a small mean particle size (217.00 ± 14.00 nm), an acceptable polydispersity index (0.28 ± 0.07), an acceptable zeta potential value (-33.60 ± 1.30 mV), and a high EGCG loading efficiency (52.08% ± 5.37%). The targeting abilities of CD44 binding were increased as the hyaluronan concentration increased and decreased by adding a competitor CD44 antibody. Moreover, we found that fucoidan treatment significantly reduced macrophage migration after lipopolysaccharide treatment in a dose-responsive manner. In summary, we successfully created macrophage-targeted nanoparticles for effective targeted delivery of EGCG, which should aid in the development of future anti-inflammatory drugs against macrophage-related diseases.

Estimation of brain functional connectivity from hypercapnia BOLD MRI data: Validation in a lifespan cohort of 170 subjects.

Functional connectivity MRI, based on Blood-Oxygenation-Level-Dependent (BOLD) signals, is typically performed while the subject is at rest. On the other hand, BOLD is also widely used in physiological imaging such as cerebrovascular reactivity (CVR) mapping using hypercapnia (HC) as a modulator. We therefore hypothesize that hypercapnia BOLD data can be used to extract FC metrics after factoring out the effects of the physiological modulation, which will allow simultaneous assessment of neural and vascular function and may be particularly important in populations such as aging and cerebrovascular diseases. The present work aims to systematically examine the feasibility of hypercapnia BOLD-based FC mapping using three commonly applied analysis methods, specifically dual-regression Independent Component Analysis (ICA), region-based FC matrix analysis, and graph-theory based network analysis, in a large cohort of 170 healthy subjects ranging from 20 to 88 years old. To validate the hypercapnia BOLD results, we also compared these FC metrics with those obtained from conventional resting-state data. ICA analysis of the hypercapnia BOLD data revealed FC maps that strongly resembled those reported in the literature. FC matrix using region-based analysis showed a correlation of 0.97 on the group-level and 0.54 ±â€¯0.10 on the individual-level, when comparing between hypercapnia and resting-state results. Although the correspondence on the individual-level was moderate, this was primarily attributed to variations intrinsic to FC mapping, because a corresponding resting-vs-resting comparison in a sub-cohort (N = 39) revealed a similar correlation of 0.57 ±â€¯0.09. Graph-theory computations were also feasible in hypercapnia BOLD data and indices of global efficiency, clustering coefficient, modularity, and segregation were successfully derived. Hypercapnia FC results revealed age-dependent differences in which within-network connections generally exhibited an age-dependent decrease while between-network connections showed an age-dependent increase.

ASL-MRICloud: An online tool for the processing of ASL MRI data.

Arterial spin labeling (ASL) MRI is increasingly used in research and clinical settings. The purpose of this work is to develop a cloud-based tool for ASL data processing, referred to as ASL-MRICloud, which may be useful to the MRI community. In contrast to existing ASL toolboxes, which are based on software installation on the user's local computer, ASL-MRICloud uses a web browser for data upload and results download, and the computation is performed on the remote server. As such, this tool is independent of the user's operating system, software version, and CPU speed. The ASL-MRICloud tool was implemented to be compatible with data acquired by scanners from all major MRI manufacturers, is capable of processing several common forms of ASL, including pseudo-continuous ASL and pulsed ASL, and can process single-delay and multi-delay ASL data. The outputs of ASL-MRICloud include absolute and relative values of cerebral blood flow, arterial transit time, voxel-wise masks indicating regions with potential hyper-perfusion and hypo-perfusion, and an image quality index. The ASL tool is also integrated with a T1 -based brain segmentation and normalization tool in MRICloud to allow generation of parametric maps in standard brain space as well as region-of-interest values. The tool was tested on a large data set containing 309 ASL scans as well as on publicly available ASL data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study.

Age-related changes in cerebrovascular reactivity and their relationship to cognition: A four-year longitudinal study.

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

Three-dimensional mapping of brain venous oxygenation using R2* oximetry.

PURPOSE: Cerebral venous oxygenation (Yv ) is an important biomarker for brain diseases. This study aims to develop an R2*-based MR oximetry that can measure cerebral Yv in 3D. METHODS: This technique separates blood signal from tissue by velocity-encoding phase contrast and measures the R2* of pure blood by multi-gradient-echo acquisition. The blood R2* was converted to Yv using an R2*-versus-oxygenation (Y) calibration curve, which was obtained by in vitro bovine blood experiments. Reproducibility, sensitivity, validity, and resolution dependence of the technique were evaluated. RESULTS: In vitro R2*-Y calibration plot revealed a strong dependence of blood R2* on oxygenation, with additional dependence on hematocrit. In vivo results demonstrated that the technique can provide a 3D venous oxygenation map that depicts both large sinuses and smaller cortical veins, with venous oxygenation ranging from 57 to 72%. Intrasession coefficient of variation of the measurement was 3.0%. The technique detected an average Yv increase of 10.8% as a result of hyperoxia, which was validated by global oxygenation measurement from T2 -Relaxation-Under-Spin-Tagging (TRUST) MRI. Two spatial resolutions, one with an isotropic voxel dimension and the other with a nonisotropic dimension, were tested for full brain coverage. CONCLUSIONS: This study demonstrated the feasibility of 3D brain oxygenation mapping without using contrast agent. Magn Reson Med 79:1304-1313, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

MRI-based measurements of whole-brain global cerebral blood flow: Comparison and validation at 1.5T and 3T.

BACKGROUND: Whole-brain global cerebral blood flow (CBF) determined by MRI techniques, calculated using total CBF (TCBF) from phase-contrast MRI (PC-MRI), and brain parenchyma volume (BPV) from T1 -weighted image, have become increasingly popular in many applications. PURPOSE/HYPOTHESIS: To determine if MRI-based measurements of whole-brain global CBF data obtained across different field strengths could be merged, TCBF and BPV data acquired at 1.5T and 3T were compared. STUDY TYPE: Prospective study. POPULATION: Seventeen healthy subjects (eight females, aged 21-29 years old). FIELD STRENGTH/SEQUENCE: Fast spoiled gradient echo (FSPGR) and PC-MRI at both 1.5T and 3T. ASSESSMENT: TCBF and BPV data acquired at 1.5T and 3T were compared. STATISTICAL TESTS: The relationships of TCBF and whole-brain global CBF between two field strengths were examined by using the Pearson correlation coefficient analysis and intraclass correlation coefficient (ICC). RESULTS: Regression analysis revealed a strong correlation between TCBF at two field strengths (R2 = 0.78, P < 0.001), and the ICC was 0.85, suggesting measurements of TCBF at 1.5T were comparable and correlated with those at 3T. There was a significant difference in BPV between field strengths, where the white matter estimate was significantly larger at 1.5T when compared with that at 3T (P < 0.001). When TCBF was further normalized to the brain parenchyma mass to obtain whole-brain global CBF, it only showed a moderate correlation between measurements at the two field strengths (R2 = 0.46, P = 0.003) and lower ICC of 0.66, reflecting the slightly higher interstrength variability in the whole-brain global CBF measurements. DATA CONCLUSION: TCBF measurements could be performed equally well with comparable results at both field strengths, but specific attention should be given when TCBF is further normalized to BPV to obtain whole-brain global CBF. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1273-1280.

Arterial-spin-labeling (ASL) perfusion MRI predicts cognitive function in elderly individuals: A 4-year longitudinal study.

BACKGROUND: With the disappointing outcomes of clinical trials on patients with Alzheimer's disease or mild cognitive impairment (MCI), there is increasing attention to understanding cognitive decline in normal elderly individuals, with the goal of identifying subjects who are most susceptible to imminent cognitive impairment. PURPOSE/HYPOTHESIS: To evaluate the potential of cerebral blood flow (CBF) as a biomarker by investigating the relationship between CBF at baseline and cognition at follow-up. STUDY TYPE: Prospective longitudinal study with a 4-year time interval. POPULATION: 309 healthy subjects aged 20-89 years old. FIELD STRENGTH/SEQUENCE: 3T pseudo-continuous-arterial-spin-labeling MRI. ASSESSMENT: CBF at baseline and cognitive assessment at both baseline and follow-up. STATISTICAL TESTS: Linear regression analyses with age, systolic blood pressure, physical activity, and baseline cognition as covariates. RESULTS: Linear regression analyses revealed that whole-brain CBF at baseline was predictive of general fluid cognition at follow-up. This effect was observed in the older group (age ≥54 years, ß = 0.221, P = 0.004), but not in younger or entire sample (ß = 0.018, P = 0.867 and ß = 0.089, P = 0.098, respectively). Among major brain lobes, frontal CBF had the highest sensitivity in predicting future cognition, with a significant effect observed for fluid cognition (ß = 0.244 P = 0.001), episodic memory (ß = 0.294, P = 0.001), and reasoning (ß = 0.186, P = 0.027). These associations remained significant after accounting for baseline cognition. Voxelwise analysis revealed that medial frontal cortex and anterior cingulate cortex, part of the default mode network (DMN), are among the most important regions in predicting fluid cognition. DATA CONCLUSION: In a healthy aging cohort, CBF can predict general cognitive ability as well as specific domains of cognitive function. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2018;48:449-458.

T1 and T2 values of human neonatal blood at 3 Tesla: Dependence on hematocrit, oxygenation, and temperature.

PURPOSE: Knowledge of blood T1 and T2 is of major importance in many applications of MRI in neonates. However, to date, there has not been a systematic study to examine neonatal blood T1/T2 relaxometry. This present study aims to investigate this topic. METHODS: Using freshly collected blood samples from human umbilical cord, we performed in vitro experiments under controlled physiological conditions to measure blood T1 and T2 at 3 Tesla (T) and their dependence on several factors, including hematocrit (Hct), oxygenation (Y) and temperature. RESULTS: The arterial T1 in neonates was 1825 ± 184 ms (Hct = 0.42 ± 0.08), longer than that of adult blood. Neonatal blood T1 was strongly dependent on Hct (P < 0.001) and Y (P = 0.005), and the dependence of T1 on Y was more prominent at higher Hct. The arterial T2 of neonatal blood was 191 ms at an Hct of 0.42, which was also longer than adult blood. Neonatal blood T2 was positively associated with blood oxygenation and negatively associated with hematocrit level, and can be characterized by an exchange model. Neonatal blood T1 was also positively associated with temperature (P < 0.001). CONCLUSION: The values provided in this report may provide important reference and calibration information for sequence optimization and quantification of in vivo neonatal MRI studies.

Simultaneous multi-slice (SMS) acquisition enhances the sensitivity of hemodynamic mapping using gas challenges.

Hemodynamic mapping using gas inhalation has received increasing interest in recent years. Cerebrovascular reactivity (CVR), which reflects the ability of the brain vasculature to dilate in response to a vasoactive stimulus, can be measured by CO2 inhalation with continuous acquisition of blood oxygen level-dependent (BOLD) magnetic resonance images. Cerebral blood volume (CBV) can be measured by O2 inhalation. These hemodynamic mapping methods are appealing because of their absence of gadolinium contrast agent, their ability to assess both baseline perfusion and vascular reserve, and their utility in calibrating the functional magnetic resonance imaging (fMRI) signal. However, like other functional and physiological indices, a major drawback of these measurements is their poor sensitivity and reliability. Simultaneous multi-slice echo planar imaging (SMS EPI) is a fast imaging technology that allows the excitation and acquisition of multiple two-dimensional slices simultaneously, and has been shown to enhance the sensitivity of several MRI applications. To our knowledge, the benefit of SMS in gas inhalation imaging has not been investigated. In this work, we compared the sensitivity of CO2 and O2 inhalation data collected using SMS factor 2 (SMS2) and SMS factor 3 (SMS3) with those collected using conventional EPI (SMS1). We showed that the sensitivity of SMS scans was significantly (p = 0.01) higher than that of conventional EPI, although no difference was found between SMS2 and SMS3 (p = 0.3). On a voxel-wise level, approximately 20-30% of voxels in the brain showed a significant enhancement in sensitivity when using SMS compared with conventional EPI, with other voxels showing an increase, but not reaching statistical significance. When using SMS, the scan duration can be reduced by half, whilst maintaining the sensitivity of conventional EPI. The availability of a sensitive acquisition technique can further enhance the potential of gas inhalation MRI in clinical applications.