Is a timely assessment of the hematocrit necessary for cardiovascular magnetic resonance-derived extracellular volume measurements?

BACKGROUND: Cardiovascular magnetic resonance (CMR)-derived extracellular volume (ECV) requires a hematocrit (Hct) to correct contrast volume distributions in blood. However, the timely assessment of Hct can be challenging and has limited the routine clinical application of ECV. The goal of the present study was to evaluate whether ECV measurements lead to significant error if a venous Hct was unavailable on the day of CMR. METHODS: 109 patients with CMR T1 mapping and two venous Hcts (Hct0: a Hct from the day of CMR, and Hct1: a Hct from a different day) were retrospectively identified. A synthetic Hct (Hctsyn) derived from native blood T1 was also assessed. The study used two different ECV methods, (1) a conventional method in which ECV was estimated from native and postcontrast T1 maps using a region-based method, and (2) an inline method in which ECV was directly measured from inline ECV mapping. ECVs measured with Hct0, Hct1, and Hctsyn were compared for each method, and the reference ECV (ECV0) was defined using the Hct0. The error between synthetic (ECVsyn) and ECV0was analyzed for the two ECV methods. RESULTS: ECV measured using Hct1 and Hctsyn were significantly correlated with ECV0 for each method. No significant differences were observed between ECV0 and ECV measured with Hct1 (ECV1; 28.4 ± 6.6% vs. 28.3 ± 6.1%, p = 0.789) and between ECV0 and ECV calculated with Hctsyn (ECVsyn; 28.4 ± 6.6% vs. 28.2 ± 6.2%, p = 0.45) using the conventional method. Similarly, ECV0 was not significantly different from ECV1 (28.5 ± 6.7% vs. 28.5 ± 6.2, p = 0.801) and ECVsyn (28.5 ± 6.7% vs. 28.4 ± 6.0, p = 0.974) using inline method. ECVsyn values revealed relatively large discrepancies in patients with lower Hcts compared with those with higher Hcts. CONCLUSIONS: Venous Hcts measured on a different day from that of the CMR examination can still be used to measure ECV. ECVsyn can provide an alternative method to quantify ECV without needing a blood sample, but significant ECV errors occur in patients with severe anemia.

A new anion exchange purification method for Cu stable isotopes in blood samples.

The isotopic composition of iron, zinc, copper, and cadmium (δ56Fe, δ66Zn, δ65Cu, and δ114Cd) are novel and promising tools to study the metabolism and homeostasis of trace metals in the human body. Serum δ65Cu has been proposed as a potential tool for diagnosis of cancer in liquid biopsy, and other metals may have similar utility. However, accurate analysis of trace metal isotopes is challenging because of the difficulties in purifying the metals from biological samples. Here we developed a simple and rapid method for sequential purification of Cu, Fe, Zn, and Cd from a single blood plasma sample. By using a combination of 11 M acetic acid and 4 M HCl in the first steps of column chemistry on AG-MP1 resin, we dramatically improve the separation of Cu from matrix elements compared to previous methods which use concentrated HCl alone. Our new method achieves full recovery of Cu, Fe, Zn, and Cd to prevent column-induced isotope fractionation effects, and effectively separates analytes from the matrix in order to reduce polyatomic interferences during isotope analysis. Our methods were verified by the analysis of isotope standards, a whole blood reference material, and a preliminary sample set including five plasma samples from healthy individuals and five plasma samples from cancer patients. This new method simplifies preparation of blood samples for metal isotope analysis, accelerating multi-isotope approaches to medical studies and contributing to our understanding of the cycling of Fe, Zn, Cu, and Cd in the human body. Graphical abstract ᅟ.

Simultaneous assessment of cerebral blood volume and diffusion heterogeneity using hybrid IVIM and DK MR imaging: initial experience with brain tumors.

OBJECTIVES: To investigate the feasibility of simultaneously assessing cerebral blood volume and diffusion heterogeneity using hybrid diffusion-kurtosis (DK) and intravoxel-incoherent-motion (IVIM) MR imaging. METHODS: Fifteen healthy volunteers and 30 patients with histologically proven brain tumours (25 WHO grade II-IV gliomas and five metastases) were recruited. On a 3-T system, diffusion-weighted imaging was performed with six b-values ranging from 0 to 1,700 s/mm2. Nonlinear least-squares fitting was employed to extract diffusion coefficient (D), diffusion kurtosis coefficient (K, a measure of the degree of non-Gaussian and heterogeneous diffusion) and intravascular volume fraction (f, a measure proportional to cerebral blood volume). Repeated-measures multivariate analysis of variance and receiver operating characteristic analysis were performed to assess the ability of D/K/f in differentiating contrast-enhanced tumour from peritumoral oedema and normal-appearing white matter. RESULTS: Based on our imaging setting (baseline signal-to-noise ratio = 32-128), coefficient of variation was 14-20 % for K, ~6 % for D and 26-44 % for f. The indexes were able to differentiate contrast-enhanced tumour (Wilks' λ = 0.026, p < 10-3), and performance was greatest with K, followed by f and D. CONCLUSIONS: Hybrid DK IVIM imaging is capable of simultaneously measuring cerebral perfusion and diffusion indexes that together may improve brain tumour diagnosis. KEY POINTS: • Hybrid DK-IVIM imaging allows simultaneous measurement of K, D and f. • Combined K/D/f better demarcates contrast-enhanced tumour than they do separately. • f correlates better with contrast-leakage-corrected CBV DSC than with uncorrected CBV DSC.

Evolutionary analysis of iron (Fe) acquisition system in Marchantia polymorpha.

To acquire appropriate iron (Fe), vascular plants have developed two unique strategies, the reduction-based strategy I of nongraminaceous plants for Fe(2+) and the chelation-based strategy II of graminaceous plants for Fe(3+) . However, the mechanism of Fe uptake in bryophytes, the earliest diverging branch of land plants and dominant in gametophyte generation is less clear. Fe isotope fractionation analysis demonstrated that the liverwort Marchantia polymorpha uses reduction-based Fe acquisition. Enhanced activities of ferric chelate reductase and proton ATPase were detected under Fe-deficient conditions. However, M. polymorpha did not show mugineic acid family phytosiderophores, the key components of strategy II, or the precursor nicotianamine. Five ZIP (ZRT/IRT-like protein) homologs were identified and speculated to be involved in Fe uptake in M. polymorpha. MpZIP3 knockdown conferred reduced growth under Fe-deficient conditions, and MpZIP3 overexpression increased Fe content under excess Fe. Thus, a nonvascular liverwort, M. polymorpha, uses strategy I for Fe acquisition. This system may have been acquired in the common ancestor of land plants and coopted from the gametophyte to sporophyte generation in the evolution of land plants.

Root-secreted nicotianamine from Arabidopsis halleri facilitates zinc hypertolerance by regulating zinc bioavailability.

Hyperaccumulators tolerate and accumulate extraordinarily high concentrations of heavy metals. Content of the metal chelator nicotianamine (NA) in the root of zinc hyperaccumulator Arabidopsis halleri is elevated compared with nonhyperaccumulators, a trait that is considered to be one of the markers of a hyperaccumulator. Using metabolite-profiling analysis of root secretions, we found that excess zinc treatment induced secretion of NA in A. halleri roots compared with the nonhyperaccumulator Arabidopsis thaliana. Metal speciation analysis further revealed that the secreted NA forms a stable complex with Zn(II). Supplying NA to a nonhyperaccumulator species markedly increased plant zinc tolerance by decreasing zinc uptake. Therefore, NA secretion from A. halleri roots facilitates zinc hypertolerance through forming a Zn(II)-NA complex outside the roots to achieve a coordinated zinc uptake rate into roots. Secretion of NA was also found to be responsible for the maintenance of iron homeostasis under excess zinc. Together our results reveal root-secretion mechanisms associated with hypertolerance and hyperaccumulation.

Caveat of measuring perfusion indexes using intravoxel incoherent motion magnetic resonance imaging in the human brain.

OBJECTIVES: To numerically and experimentally investigate the robustness of intravoxel incoherent motion (IVIM) magnetic resonance imaging in measuring perfusion indexes in the human brain. METHODS: Eighteen healthy volunteers were imaged on a 3 T clinical system. Data of IVIM imaging (12 b-values ranging from 0 to 1000 s/mm(2), 12 repetitions) were fitted with a bi-exponential model to extract blood volume fraction (f) and pseudo-diffusion coefficient (D*). The robustness of measurement was assessed by bootstrapping. Dynamic susceptibility contrast (DSC) imaging and arterial spin-labelling (ASL) imaging were performed for cross-modal comparison. Numerical simulations were performed to assess the accuracy and precision of f and D* estimates at varied signal-to-noise ratio (SNRb1000). RESULTS: Based on our experimental setting (SNRb1000 ~ 30), the average error/variability is ~5 %/25 % for f and ~100 %/30 % for D* in gray matter, and ~10 %/50 % for f and ~300 %/60 % for D* in white matter. Correlation was found between f and DSC-derived cerebral blood volume in gray matter (r = 0.29 - 0.48 across subjects, p < 10(-5)), but not in white matter. No correlation was found between f-D* product and ASL-derived cerebral blood flow. CONCLUSIONS: f may provide noninvasive measurement of cerebral blood volume, particularly in gray matter. D* has limited robustness and should be interpreted with caution. KEY POINTS: • A minimum SNR b1000 of 30 is recommended for reliable IVIM imaging. • f may provide noninvasive measurement of cerebral blood volume. • f correlates with CBV DSC in gray matter. • There is no correlation between fD* and CBF ASL . • D* has limited robustness and should be interpreted with caution.

Caffeine alters resting-state functional connectivity measured by blood oxygenation level-dependent MRI.

This study aimed to investigate the pharmacological effect of caffeine on functional connectivity measured by resting-state blood oxygenation level-dependent (BOLD) MRI in the motor cortex, visual cortex and default mode network (DMN). The protocols and procedures of the study were reviewed and approved by the Institutional Review Board of our institution. On a 3-T clinical MR system, 20 healthy volunteers underwent imaging before and after oral ingestion of a 200-mg over-the-counter caffeine pill (data from three individuals were excluded from further analysis because of excessive motion). The demographics of the remaining participants were as follows: female/male, 8/9; age, 21-35 years; non-habitual caffeine consumers over the past 6 months. Functional connectivity was calculated using the general linear model, assessed in terms of connected area (voxels) and statistical significance (Student t-values), and correlated with changes in regional cerebral blood flow as measured by arterial spin labeling MRI. Per-subject data analysis showed that caffeine decreased functional connectivity in the motor/visual cortices, but its effects on DMN varied among subjects. Correlation analysis of the changes in functional connectivity and regional blood flow suggested that the effect of caffeine on BOLD functional connectivity was predominantly neural (motor/visual cortices) and partly vascular (DMN). Group analysis showed that, after caffeine ingestion, DMN involved more attentional networks, and more extrastriate areas were integrated into the functional connectivity of the visual cortex, which may be associated with the known pharmacological effect of caffeine in elevating alertness. Caffeine consumption should thus be considered in the experimental design and data interpretation of functional connectivity studies using resting-state BOLD MRI.

A rapid procedure for isotopic purification of copper and nickel from seawater using an automated chromatography system.

BACKGROUND: Trace metals such as iron, nickel, copper, zinc, and cadmium (Fe, Ni, Cu, Zn, and Cd) are essential micronutrients (and sometimes toxins) for phytoplankton, and the analysis of trace-metal stable isotopes in seawater is a valuable tool for exploring the biogeochemical cycling of these elements in the ocean. However, the complex and often time-consuming chromatography process required to purify these elements from seawater has limited the number of trace-metal isotope samples which can be easily processed in biogeochemical studies. To facilitate the trace-metal stable isotope analysis, here, we describe a new rapid procedure that utilizes automated chromatography for extracting and purifying Ni and Cu from seawater for isotope analysis using a prepFAST-MC™ system (Elemental Scientific Inc.). RESULTS: We have tested the matrix removal effectiveness, recoveries, and procedural blanks of the new purification procedure with satisfactory results. A nearly complete recovery of Ni and a quantitative recovery of Cu are achieved. The total procedural blanks are 0.33 ± 0.24 ng for Ni and 0.42 ± 0.18 ng for Cu, which is negligible for natural seawater samples. The new procedure cleanly separates Ni and Cu from key seawater matrix elements that may cause interferences during mass spectrometry analysis. When the new procedure was used to purify seawater samples for Ni and Cu stable isotope analysis by multi-collector ICP-MS, we achieved an overall uncertainty of 0.07 ‰ for δ60Ni and 0.09 ‰ for δ65Cu (2 SD). The new purification procedure was also tested using natural seawater samples from the South Pacific, for comparison of δ60Ni and δ65Cu achieved in the same samples purified by traditional hand columns. Both methods produced similar results, and the results from both methods are consistent with analyses of δ60Ni and δ65Cu from other ocean locations as reported by other laboratories. SIGNIFICANCE: This study presents a new rapid procedure for seawater stable-metal isotope analysis by automating the chromatography step. We anticipate that the automated chromatography described here will facilitate the rapid and accurate analysis of seawater δ60Ni and δ65Cu in future studies, and may be adapted in the future to automate chromatographic purification of Fe, Zn, and Cd isotopes from seawater.

Quantification of Abdominal Muscle Mass and Diagnosis of Sarcopenia with Cross-Sectional Imaging in Patients with Polycystic Kidney Disease: Correlation with Total Kidney Volume.

Background: Polycystic kidney disease (PKD) is an inherited disorder characterized by renal cysts that may mask lean body loss. This study quantified and compared muscle mass by using computed tomography (CT) and magnetic resonance imaging (MRI) images between the PKD and control groups and correlated muscle mass with total kidney volume (TKV). Methods: We retrospectively enrolled patients who had a new diagnosis of PKD from May 2015 to May 2016. The CT and MRI images at the third lumbar level were processed to measure the total abdominal muscle (TAM) area for the diagnosis of sarcopenia, and TKV was estimated using the ellipsoid formula. Results: We included 37 women and 25 men (mean age: 50.40 years) in the PKD group. There was no difference in body mass index and albumin levels, but significant differences in creatinine level (p < 0.001), TAM area (p = 0.047), and TKV (p < 0.001), were noted between the two groups. A significantly negative correlation was observed between TKV and TAM area after adjustment for body height (r = −0.217, p = 0.003). Conclusions: CT and MRI images can accurately diagnose sarcopenia, which may be masked by cysts in patients with PKD.

Pseudocontinuous arterial spin labeling perfusion magnetic resonance imaging--a normative study of reproducibility in the human brain.

Pseudocontinuous arterial spin labeling (PCASL), a newly proposed perfusion magnetic resonance imaging (MRI) technique, has the potential of providing a better balance between labeling efficiency and signal-to-noise ratio than conventional ASL methods. The advantage will not be exploitable until adequate reproducibility can be achieved. In this study, we investigated the reproducibility of PCASL on twelve healthy volunteers by taking into account the inclusion of correction for coil sensitivity (CS) and labeling efficiency (α). Each subject underwent two identical sessions scheduled two weeks apart. For comparison, pulsed ASL (PASL) imaging was also conducted using the flow-sensitive alternating inversion recovery method. MR imaging was performed on a 3T whole body system using a 12-channel phased array for reception. Blood flow was quantified for gray matter and assessed globally as well as in the flow territories of the internal carotid arteries and posterior cerebral arteries. Experimental results showed that CS accounted for 35% and 60% of inter-session variability in PCASL and PASL, respectively. With CS correction alone, coefficient of variance (CV) remained larger with PCASL than PASL (p=0.02). CV was 12% with CS-corrected PASL and 11% with PCASL when CS and α were corrected for in conjunction. We concluded that CS correction is necessary for ASL imaging when using phased array receiver and that after CS correction, PCASL requires α correction to provide reproducibility comparable to PASL.

CMR-derived ECVs vary with myocardial region and associate with the regional wall thickness.

This study was designed to identify whether the position and size of the region of interest (ROI) influence extracellular volume fraction (ECV) measurements. Patients with localized (n = 203) or infiltrative (n = 215) cardiomyopathies and 36 normal controls were enrolled in this study. ECV measurements at 4 different regions, including the anterior, septal, posterior and lateral wall regions, were measured, and all groups were compared. Regional ECV was correlated with the corresponding regional wall thickness. The diagnostic power to differentiate the myocardial abnormalities was evaluated for each myocardial region. ECVs measured using five different ROI sizes within each myocardial region were compared. Our results showed that ECVs varied among the myocardial regions, and this variation was significantly associated with regional wall thicknesses. For the detection of myocardial abnormalities, regional ECV revealed similar results as ECV derived from the whole region except for the anterior region. No significant difference was found in the ECVs measured using the five different ROI sizes. In conclusion, CMR-derived ECVs vary with myocardial region, and this variation is significantly associated with the regional wall thickness. In contrast, the measured size of the ROI has less of an effect on the ECV.

Toward quantitative fast diffusion kurtosis imaging with b-values chosen in consideration of signal-to-noise ratio and model fidelity.

PURPOSE: Diffusion kurtosis (DK) imaging is a variant of conventional diffusion magnetic resonance (MR) imaging that allows assessment of non-Gaussian diffusion. Fast DK imaging expedites the procedure by decreasing both scan time (acquiring the minimally required number of b-values) and computation time (obviating least-square curve fitting). This study aimed to investigate the applicability of fast DK imaging for both cerebral gray matter and white matter as a quantitative method. METHODS: Seventeen healthy volunteers were recruited and each provided written informed consent before participation. On a 3-Tesla clinical MR system, diffusion imaging was performed with 12 b-values ranging from 0 to 4000 s/mm2 . Diffusion encoding was along three orthogonal directions (slice selection, phase encoding, and frequency encoding) in separate series. Candidate b-values were chosen by first determining the maximum b-value (bmax ) in the context of signal-to-noise ratio and then assessing the model fidelity for all b-value combinations within bmax . Diffusion coefficient (D) and diffusion kurtosis coefficient (K) were derived from these candidates and assessed for their dependence on b-value combination. RESULTS: Our data suggested bmax to be 2200 s/mm2 as a trade-off between the percentage (~80%) of voxels statistically detectable against background and the sensitivity to non-Gaussian diffusion in both gray matter and white matter. The measurement dependence on b-value was observed predominantly in areas with a considerable amount of cerebrospinal fluid. In most gray matter and white matter, b-value combinations do not cause statistical difference in the calculated D and K. CONCLUSIONS: For fast DK imaging to be quantitatively applicable in both gray matter and white matter, bmax should be chosen to ensure adequate signal-to-noise ratio in the majority of gray/white matter and the two nonzero b-values should be chosen in consideration of model fidelity to mitigate the dependence of derived indices on b-values.

Alterations of cerebral perfusion in asymptomatic internal carotid artery steno-occlusive disease.

Patients with asymptomatic occlusion in the internal carotid arteries (ICA) have been shown to have a better preserved hemodynamic status of the brain as compared to patients with symptoms. This study was aimed to explore the cerebral perfusion alterations in asymptomatic patients using multi-parametric arterial spin-labeling (ASL) magnetic resonance (MR) imaging. Forty-two patients diagnosed with asymptomatic ICA stenosis/occlusion were prospectively included and divided into high-grade (ultrasonographic stenosis ≥70%, N = 20) and low-grade groups (N = 22). On a 3-Tesla clinical MR scanner, pseudo-continuous ASL was performed to measure cerebral blood flow CBF, arterial transit time ATT, and flow territory. Fisher's exact test indicates that the high-grade group has higher frequency in asymmetric ATT (p < 10-3) and asymmetric flow territory (p < 10-3) as compared to the low-grade group. The between-group difference in CBF asymmetry is marginal (p = 0.062). Logistic regression further reveals that hemispherical asymmetry in ATT and flow territory is associated with the existence of high-grade ICA stenosis (odds ratio = 12 and 21, respectively), whereas hemispherical asymmetry in CBF is not. Our data suggest that ATT and flow territory may be better predictors of asymptomatic high-grade ICA stenosis diagnosed by carotid ultrasonography than CBF.