Quantification of water exchange across the blood-brain barrier using noncontrast MR fingerprinting.

PURPOSE: A method is proposed to quantify cerebral blood volume ( v b $$ {v}_b $$ ) and intravascular water residence time ( τ b $$ {\tau}_b $$ ) using MR fingerprinting (MRF), applied using a spoiled gradient echo sequence without the need for contrast agent. METHODS: An in silico study optimized an acquisition protocol to maximize the sensitivity of the measurement to v b $$ {v}_b $$ and τ b $$ {\tau}_b $$ changes. Its accuracy in the presence of variations in T 1 , t $$ {\mathrm{T}}_{1,t} $$ , T 1 , b $$ {\mathrm{T}}_{1,b} $$ , and B 1 $$ {\mathrm{B}}_1 $$ was evaluated. The optimized protocol (scan time of 19 min) was then tested in a exploratory healthy volunteer study (10 volunteers, mean age 24 ± $$ \pm $$ 3, six males) at 3 T with a repeat scan taken after repositioning to allow estimation of repeatability. RESULTS: Simulations show that assuming literature values for T 1 , b $$ {\mathrm{T}}_{1,b} $$ and T 1 , t $$ {\mathrm{T}}_{1,t} $$ , no variation in B 1 $$ {\mathrm{B}}_1 $$ , while fitting only v b $$ {v}_b $$ and τ b $$ {\tau}_b $$ , leads to large errors in quantification of v b $$ {v}_b $$ and τ b $$ {\tau}_b $$ , regardless of noise levels. However, simulations also show that matching T 1 , t $$ {\mathrm{T}}_{1,t} $$ , T 1 , b $$ {\mathrm{T}}_{1,b} $$ , B 1 + $$ {\mathrm{B}}_1^{+} $$ , v b $$ {v}_b $$ and τ b $$ {\tau}_b $$ , simultaneously is feasible at clinically achievable noise levels. Across the healthy volunteers, all parameter quantifications fell within the expected literature range. In addition, the maps show good agreement between hemispheres suggesting physiologically relevant information is being extracted. Expected differences between white and gray matter T 1 , t $$ {\mathrm{T}}_{1,t} $$ (p < 0.0001) and v b $$ {v}_b $$ (p < 0.0001) are observed, T 1 , b $$ {\mathrm{T}}_{1,b} $$ and τ b $$ {\tau}_b $$ show no significant differences, p = 0.4 and p = 0.6, respectively. Moderate to excellent repeatability was seen between repeat scans: mean intra-class correlation coefficient of T 1 , t : 0 . 91 $$ {\mathrm{T}}_{1,t}:0.91 $$ , T 1 , b : 0 . 58 $$ {\mathrm{T}}_{1,b}:0.58 $$ , v b : 0 . 90 $$ {v}_b:0.90 $$ , and τ b : 0 . 96 $$ {\tau}_b:0.96 $$ . CONCLUSION: We demonstrate that regional simultaneous quantification of v b $$ {v}_b $$ , τ b $$ {\tau}_b $$ , T 1 , b , T 1 , t $$ {\mathrm{T}}_{1,b},{T}_{1,t} $$ , and B 1 + $$ {\mathrm{B}}_1^{+} $$ using MRF is feasible in vivo.

Independent component analysis (ICA) applied to dynamic oxygen-enhanced MRI (OE-MRI) for robust functional lung imaging at 3 T.

PURPOSE: Dynamic lung oxygen-enhanced MRI (OE-MRI) is challenging due to the presence of confounding signals and poor signal-to-noise ratio, particularly at 3 T. We have created a robust pipeline utilizing independent component analysis (ICA) to automatically extract the oxygen-induced signal change from confounding factors to improve the accuracy and sensitivity of lung OE-MRI. METHODS: Dynamic OE-MRI was performed on healthy participants using a dual-echo multi-slice spoiled gradient echo sequence at 3 T and cyclical gas delivery. ICA was applied to each echo within a thoracic mask. The ICA component relating to the oxygen-enhancement signal was automatically identified using correlation analysis. The oxygen-enhancement component was reconstructed, and the percentage signal enhancement (PSE) was calculated. The lung PSE of current smokers was compared with nonsmokers; scan-rescan repeatability, ICA pipeline repeatability, and reproducibility between two vendors were assessed. RESULTS: ICA successfully extracted a consistent oxygen-enhancement component for all participants. Lung tissue and oxygenated blood displayed the opposite oxygen-induced signal enhancements. A significant difference in PSE was observed between the lungs of current smokers and nonsmokers. The scan-rescan repeatability and the ICA pipeline repeatability were good. CONCLUSION: The developed pipeline demonstrated sensitivity to the signal enhancements of the lung tissue and oxygenated blood at 3 T. The difference in lung PSE between current smokers and nonsmokers indicates a likely sensitivity to lung function alterations that may be seen in mild pathology, supporting future use of our methods in patient studies.

Feasibility of dynamic T2 *-based oxygen-enhanced lung MRI at 3T.

PURPOSE: To demonstrate proof-of-concept of a T2 *-sensitized oxygen-enhanced MRI (OE-MRI) method at 3T by assessing signal characteristics, repeatability, and reproducibility of dynamic lung OE-MRI metrics in healthy volunteers. METHODS: We performed sequence-specific simulations for protocol optimisation and acquired free-breathing OE-MRI data from 16 healthy subjects using a dual-echo RF-spoiled gradient echo approach at 3T across two institutions. Non-linear registration and tissue density correction were applied. Derived metrics included percent signal enhancement (PSE), ∆R2 * and wash-in time normalized for breathing rate (τ-nBR). Inter-scanner reproducibility and intra-scanner repeatability were evaluated using intra-class correlation coefficient (ICC), repeatability coefficient, reproducibility coefficient, and Bland-Altman analysis. RESULTS: Simulations and experimental data show negative contrast upon oxygen inhalation, due to substantial dominance of ∆R2 * at TE > 0.2 ms. Density correction improved signal fluctuations. Density-corrected mean PSE values, aligned with simulations, display TE-dependence, and an anterior-to-posterior PSE reduction trend at TE1 . ∆R2 * maps exhibit spatial heterogeneity in oxygen delivery, featuring anterior-to-posterior R2 * increase. Mean T2 * values across 32 scans were 0.68 and 0.62 ms for pre- and post-O2 inhalation, respectively. Excellent or good agreement emerged from all intra-, inter-scanner and inter-rater variability tests for PSE and ∆R2 *. However, ICC values for τ-nBR demonstrated limited agreement between repeated measures. CONCLUSION: Our results demonstrate the feasibility of a T2 *-weighted method utilizing a dual-echo RF-spoiled gradient echo approach, simultaneously capturing PSE, ∆R2 * changes, and oxygen wash-in during free-breathing. The excellent or good repeatability and reproducibility on intra- and inter-scanner PSE and ∆R2 * suggest potential utility in multi-center clinical applications.

The ISMRM Open Science Initiative for Perfusion Imaging (OSIPI): Results from the OSIPI-Dynamic Contrast-Enhanced challenge.

PURPOSE: K trans $$ {K}^{\mathrm{trans}} $$ has often been proposed as a quantitative imaging biomarker for diagnosis, prognosis, and treatment response assessment for various tumors. None of the many software tools for K trans $$ {K}^{\mathrm{trans}} $$ quantification are standardized. The ISMRM Open Science Initiative for Perfusion Imaging-Dynamic Contrast-Enhanced (OSIPI-DCE) challenge was designed to benchmark methods to better help the efforts to standardize K trans $$ {K}^{\mathrm{trans}} $$ measurement. METHODS: A framework was created to evaluate K trans $$ {K}^{\mathrm{trans}} $$ values produced by DCE-MRI analysis pipelines to enable benchmarking. The perfusion MRI community was invited to apply their pipelines for K trans $$ {K}^{\mathrm{trans}} $$ quantification in glioblastoma from clinical and synthetic patients. Submissions were required to include the entrants' K trans $$ {K}^{\mathrm{trans}} $$ values, the applied software, and a standard operating procedure. These were evaluated using the proposed OSIP I gold $$ \mathrm{OSIP}{\mathrm{I}}_{\mathrm{gold}} $$ score defined with accuracy, repeatability, and reproducibility components. RESULTS: Across the 10 received submissions, the OSIP I gold $$ \mathrm{OSIP}{\mathrm{I}}_{\mathrm{gold}} $$ score ranged from 28% to 78% with a 59% median. The accuracy, repeatability, and reproducibility scores ranged from 0.54 to 0.92, 0.64 to 0.86, and 0.65 to 1.00, respectively (0-1 = lowest-highest). Manual arterial input function selection markedly affected the reproducibility and showed greater variability in K trans $$ {K}^{\mathrm{trans}} $$ analysis than automated methods. Furthermore, provision of a detailed standard operating procedure was critical for higher reproducibility. CONCLUSIONS: This study reports results from the OSIPI-DCE challenge and highlights the high inter-software variability within K trans $$ {K}^{\mathrm{trans}} $$ estimation, providing a framework for ongoing benchmarking against the scores presented. Through this challenge, the participating teams were ranked based on the performance of their software tools in the particular setting of this challenge. In a real-world clinical setting, many of these tools may perform differently with different benchmarking methodology.

Blood-brain barrier water exchange measurements using contrast-enhanced ASL.

A technique for quantifying regional blood-brain barrier (BBB) water exchange rates using contrast-enhanced arterial spin labelling (CE-ASL) is presented and evaluated in simulations and in vivo. The two-compartment ASL model describes the water exchange rate from blood to tissue, k b , but to estimate k b in practice it is necessary to separate the intra- and extravascular signals. This is challenging in standard ASL data owing to the small difference in T 1 values. Here, a gadolinium-based contrast agent is used to increase this T 1 difference and enable the signal components to be disentangled. The optimal post-contrast blood T 1 ( T 1 , b post ) at 3 T was determined in a sensitivity analysis, and the accuracy and precision of the method quantified using Monte Carlo simulations. Proof-of-concept data were acquired in six healthy volunteers (five female, age range 24-46 years). The sensitivity analysis identified the optimal T 1 , b post at 3 T as 0.8 s. Simulations showed that k b could be estimated in individual cortical regions with a relative error ϵ < 1 % and coefficient of variation CoV = 30 %; however, a high dependence on blood T 1 was also observed. In volunteer data, mean parameter values in grey matter were: arterial transit time t A = 1 . 15 ± 0 . 49 s, cerebral blood flow f = 58 . 0 ± 14 . 3 mL blood/min/100 mL tissue and water exchange rate k b = 2 . 32 ± 2 . 49 s-1 . CE-ASL can provide regional BBB water exchange rate estimates; however, the clinical utility of the technique is dependent on the achievable accuracy of measured T 1 values.

Mitochondrial uniparental inheritance achieved after fertilization challenges the nuclear-cytoplasmic conflict hypothesis for anisogamy evolution.

In eukaryotes, a fundamental phenomenon underlying sexual selection is the evolution of gamete size dimorphism between the sexes (anisogamy) from an ancestral gametic system with gametes of the same size in both mating types (isogamy). The nuclear-cytoplasmic conflict hypothesis has been one of the major theoretical hypotheses for the evolution of anisogamy. It proposes that anisogamy evolved as an adaptation for preventing nuclear-cytoplasmic conflict by minimizing male gamete size to inherit organelles uniparentally. In ulvophycean green algae, biparental inheritance of organelles is observed in isogamous species, as the hypothesis assumes. So we tested the hypothesis by examining whether cytoplasmic inheritance is biparental in Monostroma angicava, a slightly anisogamous ulvophycean that produces large male gametes. We tracked the fates of mitochondria in intraspecific crosses with PCR-RFLP markers. We confirmed that mitochondria are maternally inherited. However, paternal mitochondria enter the zygote, where their DNA can be detected for over 14 days. This indicates that uniparental inheritance is enforced by eliminating paternal mitochondrial DNA in the zygote, rather than by decreasing male gamete size to the minimum. Thus, uniparental cytoplasmic inheritance is achieved by an entirely different mechanism, and is unlikely to drive the evolution of anisogamy in ulvophyceans.

Imaging human lung perfusion with contrast media: A meta-analysis.

PURPOSE: To pool and summarise published data of pulmonary blood flow (PBF), pulmonary blood volume (PBV) and mean transit time (MTT) of the human lung, obtained with perfusion MRI or CT to provide reliable reference values of healthy lung tissue. In addition, the available data regarding diseased lung was investigated. METHODS: PubMed was systematically searched to identify studies that quantified PBF/PBV/MTT in the human lung by injection of contrast agent, imaged by MRI or CT. Only data analysed by 'indicator dilution theory' were considered numerically. Weighted mean (wM), weighted standard deviation (wSD) and weighted coefficient of variance (wCoV) were obtained for healthy volunteers (HV), weighted according to the size of the datasets. Signal to concentration conversion method, breath holding method and presence of 'pre-bolus' were noted. RESULTS: PBV was obtained from 313 measurements from 14 publications (wM: 13.97 ml/100 ml, wSD: 4.21 ml/100 ml, wCoV 0.30). MTT was obtained from 188 measurements from 10 publications (wM: 5.91 s, wSD: 1.84 s wCoV 0.31). PBF was obtained from 349 measurements from 14 publications (wM: 246.26 ml/100 ml ml/min, wSD: 93.13 ml/100 ml ml/min, wCoV 0.38). PBV and PBF were higher when the signal was normalised than when it was not. No significant differences were found for PBV and PBF between breathing states or between pre-bolus and no pre-bolus. Data for diseased lung were insufficient for meta-analysis. CONCLUSION: Reference values for PBF, MTT and PBV were obtained in HV. The literature data are insufficient to draw strong conclusions regarding disease reference values.

Filter exchange imaging with crusher gradient modelling detects increased blood-brain barrier water permeability in response to mild lung infection.

Blood-brain barrier (BBB) dysfunction occurs in many brain diseases, and there is increasing evidence to suggest that it is an early process in dementia which may be exacerbated by peripheral infection. Filter-exchange imaging (FEXI) is an MRI technique for measuring trans-membrane water exchange. FEXI data is typically analysed using the apparent exchange rate (AXR) model, yielding estimates of the AXR. Crusher gradients are commonly used to remove unwanted coherence pathways arising from longitudinal storage pulses during the mixing period. We first demonstrate that when using thin slices, as is needed for imaging the rodent brain, crusher gradients result in underestimation of the AXR. To address this, we propose an extended crusher-compensated exchange rate (CCXR) model to account for diffusion-weighting introduced by the crusher gradients, which is able to recover ground truth values of BBB water exchange (kin) in simulated data. When applied to the rat brain, kin estimates obtained using the CCXR model were 3.10 s-1 and 3.49 s-1 compared to AXR estimates of 1.24 s-1 and 0.49 s-1 for slice thicknesses of 4.0 mm and 2.5 mm respectively. We then validated our approach using a clinically relevant Streptococcus pneumoniae lung infection. We observed a significant 70 ± 10% increase in BBB water exchange in rats during active infection (kin = 3.78 ± 0.42 s-1) compared to before infection (kin = 2.72 ± 0.30 s-1; p = 0.02). The BBB water exchange rate during infection was associated with higher levels of plasma von Willebrand factor (VWF), a marker of acute vascular inflammation. We also observed 42% higher expression of perivascular aquaporin-4 (AQP4) in infected animals compared to non-infected controls, while levels of tight junction proteins remain consistent between groups. In summary, we propose a modelling approach for FEXI data which removes the bias in estimated water-exchange rates associated with the use of crusher gradients. Using this approach, we demonstrate the impact of peripheral infection on BBB water exchange, which appears to be mediated by endothelial dysfunction and associated with an increase in perivascular AQP4.

First-in-human technique translation of oxygen-enhanced MRI to an MR Linac system in patients with head and neck cancer.

BACKGROUND AND PURPOSE: Tumour hypoxia is prognostic in head and neck cancer (HNC), associated with poor loco-regional control, poor survival and treatment resistance. The advent of hybrid MRI - radiotherapy linear accelerator or 'MR Linac' systems - could permit imaging for treatment adaptation based on hypoxic status. We sought to develop oxygen-enhanced MRI (OE-MRI) in HNC and translate the technique onto an MR Linac system. MATERIALS AND METHODS: MRI sequences were developed in phantoms and 15 healthy participants. Next, 14 HNC patients (with 21 primary or local nodal tumours) were evaluated. Baseline tissue longitudinal relaxation time (T1) was measured alongside the change in 1/T1 (termed ΔR1) between air and oxygen gas breathing phases. We compared results from 1.5 T diagnostic MR and MR Linac systems. RESULTS: Baseline T1 had excellent repeatability in phantoms, healthy participants and patients on both systems. Cohort nasal concha oxygen-induced ΔR1 significantly increased (p < 0.0001) in healthy participants demonstrating OE-MRI feasibility. ΔR1 repeatability coefficients (RC) were 0.023-0.040 s-1 across both MR systems. The tumour ΔR1 RC was 0.013 s-1 and the within-subject coefficient of variation (wCV) was 25% on the diagnostic MR. Tumour ΔR1 RC was 0.020 s-1 and wCV was 33% on the MR Linac. ΔR1 magnitude and time-course trends were similar on both systems. CONCLUSION: We demonstrate first-in-human translation of volumetric, dynamic OE-MRI onto an MR Linac system, yielding repeatable hypoxia biomarkers. Data were equivalent on the diagnostic MR and MR Linac systems. OE-MRI has potential to guide future clinical trials of biology guided adaptive radiotherapy.

The early rise and spread of evolutionary game theory: perspectives based on recollections of early workers.

Though the first attempts to introduce game theory into evolutionary biology failed, new formalism by Maynard Smith and Price in 1973 had almost instant success. We use information supplied by early workers to analyse how and why evolutionary game theory (EGT) spread so rapidly in its earliest years. EGT was a major tool for the rapidly expanding discipline of behavioural ecology in the 1970s; each catalysed the other. The first models were applied to animal contests, and early workers sought to improve their biological reality to compare predictions with observations. Furthermore, it was quickly realized that EGT provided a general evolutionary modelling method; not only was it swiftly applied to diverse phenotypic adaptations in evolutionary biology, it also attracted researchers from other disciplines such as mathematics and economics, for which game theory was first devised. Lastly, we pay attention to exchanges with population geneticists, considering tensions between the two modelling methods, as well as efforts to bring them closer. This article is part of the theme issue 'Half a century of evolutionary games: a synthesis of theory, application and future directions'.

Cardiac q-space trajectory imaging by motion-compensated tensor-valued diffusion encoding in human heart in vivo.

PURPOSE: Tensor-valued diffusion encoding can probe more specific features of tissue microstructure than what is available by conventional diffusion weighting. In this work, we investigate the technical feasibility of tensor-valued diffusion encoding at high b-values with q-space trajectory imaging (QTI) analysis, in the human heart in vivo. METHODS: Ten healthy volunteers were scanned on a 3T scanner. We designed time-optimal gradient waveforms for tensor-valued diffusion encoding (linear and planar) with second-order motion compensation. Data were analyzed with QTI. Normal values and repeatability were investigated for the mean diffusivity (MD), fractional anisotropy (FA), microscopic FA (µFA), isotropic, anisotropic and total mean kurtosis (MKi, MKa, and MKt), and orientation coherence (Cc ). A phantom, consisting of two fiber blocks at adjustable angles, was used to evaluate sensitivity of parameters to orientation dispersion and diffusion time. RESULTS: QTI data in the left ventricular myocardium were MD = 1.62 ± 0.07 µm2 /ms, FA = 0.31 ± 0.03, µFA = 0.43 ± 0.07, MKa = 0.20 ± 0.07, MKi = 0.13 ± 0.03, MKt = 0.33 ± 0.09, and Cc  = 0.56 ± 0.22 (mean ± SD across subjects). Phantom experiments showed that FA depends on orientation dispersion, whereas µFA was insensitive to this effect. CONCLUSION: We demonstrated the first tensor-valued diffusion encoding and QTI analysis in the heart in vivo, along with first measurements of myocardial µFA, MKi, MKa, and Cc . The methodology is technically feasible and provides promising novel biomarkers for myocardial tissue characterization.

Blood-brain barrier water exchange measurements using FEXI: Impact of modeling paradigm and relaxation time effects.

PURPOSE: To evaluate potential modeling paradigms and the impact of relaxation time effects on human blood-brain barrier (BBB) water exchange measurements using FEXI (BBB-FEXI), and to quantify the accuracy, precision, and repeatability of BBB-FEXI exchange rate estimates at 3 T $$ \mathrm{T} $$ . METHODS: Three modeling paradigms were evaluated: (i) the apparent exchange rate (AXR) model; (ii) a two-compartment model ( 2 CM $$ 2\mathrm{CM} $$ ) explicitly representing intra- and extravascular signal components, and (iii) a two-compartment model additionally accounting for finite compartmental T 1 $$ {\mathrm{T}}_1 $$ and T 2 $$ {\mathrm{T}}_2 $$ relaxation times ( 2 CM r $$ 2{\mathrm{CM}}_r $$ ). Each model had three free parameters. Simulations quantified biases introduced by the assumption of infinite relaxation times in the AXR and 2 CM $$ 2\mathrm{CM} $$ models, as well as the accuracy and precision of all three models. The scan-rescan repeatability of all paradigms was quantified for the first time in vivo in 10 healthy volunteers (age range 23-52 years; five female). RESULTS: The assumption of infinite relaxation times yielded exchange rate errors in simulations up to 42%/14% in the AXR/ 2 CM $$ 2\mathrm{CM} $$ models, respectively. Accuracy was highest in the compartmental models; precision was best in the AXR model. Scan-rescan repeatability in vivo was good for all models, with negligible bias and repeatability coefficients in grey matter of RC AXR = 0 . 43 $$ {\mathrm{RC}}_{\mathrm{AXR}}=0.43 $$ s - 1 $$ {\mathrm{s}}^{-1} $$ , RC 2 CM = 0 . 51 $$ {\mathrm{RC}}_{2\mathrm{CM}}=0.51 $$ s - 1 $$ {\mathrm{s}}^{-1} $$ , and RC 2 CM r = 0 . 61 $$ {\mathrm{RC}}_{2{\mathrm{CM}}_r}=0.61 $$ s - 1 $$ {\mathrm{s}}^{-1} $$ . CONCLUSION: Compartmental modelling of BBB-FEXI signals can provide accurate and repeatable measurements of BBB water exchange; however, relaxation time and partial volume effects may cause model-dependent biases.

Imaging biomarkers of lung ventilation in interstitial lung disease from 129Xe and oxygen enhanced 1H MRI.

PURPOSE: To compare imaging biomarkers from hyperpolarised 129Xe ventilation MRI and dynamic oxygen-enhanced MRI (OE-MRI) with standard pulmonary function tests (PFT) in interstitial lung disease (ILD) patients. To evaluate if biomarkers can separate ILD subtypes and detect early signs of disease resolution or progression. STUDY TYPE: Prospective longitudinal. POPULATION: Forty-one ILD (fourteen idiopathic pulmonary fibrosis (IPF), eleven hypersensitivity pneumonitis (HP), eleven drug-induced ILD (DI-ILD), five connective tissue disease related-ILD (CTD-ILD)) patients and ten healthy volunteers imaged at visit 1. Thirty-four ILD patients completed visit 2 (eleven IPF, eight HP, ten DIILD, five CTD-ILD) after 6 or 26 weeks. FIELD STRENGTH/SEQUENCE: MRI was performed at 1.5 T, including inversion recovery T1 mapping, dynamic MRI acquisition with varying oxygen levels, and hyperpolarised 129Xe ventilation MRI. Subjects underwent standard spirometry and gas transfer testing. ASSESSMENT: Five 1H MRI and two 129Xe MRI ventilation metrics were compared with spirometry and gas transfer measurements. STATISTICAL TEST: To evaluate differences at visit 1 among subgroups: ANOVA or Kruskal-Wallis rank tests with correction for multiple comparisons. To assess the relationships between imaging biomarkers, PFT, age and gender, at visit 1 and for the change between visit 1 and 2: Pearson correlations and multilinear regression models. RESULTS: The global PFT tests could not distinguish ILD subtypes. Percentage ventilated volumes were lower in ILD patients than in HVs when measured with 129Xe MRI (HV 97.4 ± 2.6, CTD-ILD: 91.0 ± 4.8 p = 0.017, DI-ILD 90.1 ± 7.4 p = 0.003, HP 92.6 ± 4.0 p = 0.013, IPF 88.1 ± 6.5 p < 0.001), but not with OE-MRI. 129Xe reported more heterogeneous ventilation in DI-ILD and IPF than in HV, and OE-MRI reported more heterogeneous ventilation in DI-ILD and IPF than in HP or CTD-ILD. The longitudinal changes reported by the imaging biomarkers did not correlate with the PFT changes between visits. DATA CONCLUSION: Neither 129Xe ventilation nor OE-MRI biomarkers investigated in this study were able to differentiate between ILD subtypes, suggesting that ventilation-only biomarkers are not indicated for this task. Limited but progressive loss of ventilated volume as measured by 129Xe-MRI may be present as the biomarker of focal disease progresses. OE-MRI biomarkers are feasible in ILD patients and do not correlate strongly with PFT. Both OE-MRI and 129Xe MRI revealed more spatially heterogeneous ventilation in DI-ILD and IPF.

Direct jet coaxial electrospinning of axon-mimicking fibers for diffusion tensor imaging.

Hollow polymer microfibers with variable microstructural and hydrophilic properties were proposed as building elements to create axon-mimicking phantoms for validation of diffusion tensor imaging (DTI). The axon-mimicking microfibers were fabricated in a mm-thick 3D anisotropic fiber strip, by direct jet coaxial electrospinning of PCL/polysiloxane-based surfactant (PSi) mixture as shell and polyethylene oxide (PEO) as core. Hydrophilic PCL-PSi fiber strips were first obtained by carefully selecting appropriate solvents for the core and appropriate fiber collector rotating and transverse speeds. The porous cross-section and anisotropic orientation of axon-mimicking fibers were then quantitatively evaluated using two ImageJ plugins-nearest distance (ND) and directionality based on their scanning electron microscopy (SEM) images. Third, axon-mimicking phantom was constructed from PCL-PSi fiber strips with variable porous-section and fiber orientation and tested on a 3T clinical MR scanner. The relationship between DTI measurements (mean diffusivity [MD] and fractional anisotropy [FA]) of phantom samples and their pore size and fiber orientation was investigated. Two key microstructural parameters of axon-mimicking phantoms including normalized pore distance and dispersion of fiber orientation could well interpret the variations in DTI measurements. Two PCL-PSi phantom samples made from different regions of the same fiber strips were found to have similar MD and FA values, indicating that the direct jet coaxial electrospun fiber strips had consistent microstructure. More importantly, the MD and FA values of the developed axon-mimicking phantoms were mostly in the biologically relevant range.

Clinical indications and acquisition protocol for the use of dynamic contrast-enhanced MRI in head and neck cancer squamous cell carcinoma: recommendations from an expert panel.

BACKGROUND: The clinical role of perfusion-weighted MRI (PWI) in head and neck squamous cell carcinoma (HNSCC) remains to be defined. The aim of this study was to provide evidence-based recommendations for the use of PWI sequence in HNSCC with regard to clinical indications and acquisition parameters. METHODS: Public databases were searched, and selected papers evaluated applying the Oxford criteria 2011. A questionnaire was prepared including statements on clinical indications of PWI as well as its acquisition technique and submitted to selected panelists who worked in anonymity using a modified Delphi approach. Each panelist was asked to rate each statement using a 7-point Likert scale (1 = strongly disagree, 7 = strongly agree). Statements with scores equal or inferior to 5 assigned by at least two panelists were revised and re-submitted for the subsequent Delphi round to reach a final consensus. RESULTS: Two Delphi rounds were conducted. The final questionnaire consisted of 6 statements on clinical indications of PWI and 9 statements on the acquisition technique of PWI. Four of 19 (21%) statements obtained scores equal or inferior to 5 by two panelists, all dealing with clinical indications. The Delphi process was considered concluded as reasons entered by panelists for lower scores were mainly related to the lack of robust evidence, so that no further modifications were suggested. CONCLUSIONS: Evidence-based recommendations on the use of PWI have been provided by an independent panel of experts worldwide, encouraging a standardized use of PWI across university and research centers to produce more robust evidence.

Clinical translation of quantitative magnetic resonance imaging biomarkers - An overview and gap analysis of current practice.

PURPOSE: This overview of the current landscape of quantitative magnetic resonance imaging biomarkers (qMR IBs) aims to support the standardisation of academic IBs to assist their translation to clinical practice. METHODS: We used three complementary approaches to investigate qMR IB use and quality management practices within the UK: 1) a literature search of qMR and quality management terms during 2011-2015 and 2016-2020; 2) a database search for clinical research studies using qMR IBs during 2016-2020; and 3) a survey to ascertain the current availability and quality management practices for clinical MRI scanners and associated equipment at research institutions across the UK. RESULTS: The analysis showed increased use of all qMR methods between the periods 2011-2015 and 2016-2020 and diffusion-tensor MRI and volumetry to be popular methods. However, the "translation ratio" of journal articles to clinical research studies was higher for qMR methods that have evidence of clinical translation via a commercial route, such as fat fraction and T2 mapping. The number of journal articles citing quality management terms doubled between the periods 2011-2015 and 2016-2020; although, its proportion relative to all journal articles only increased by 3.0%. The survey suggested that quality assurance (QA) and quality control (QC) of data acquisition procedures are under-reported in the literature and that QA/QC of acquired data/data analysis are under-developed and lack consistency between institutions. CONCLUSIONS: We summarise current attempts to standardise and translate qMR IBs, and conclude by outlining the ideal quality management practices and providing a gap analysis between current practice and a metrological standard.

Adaptive division of growth and development between hosts in helminths with two-host life cycles.

Parasitic worms (helminths) with complex life cycles divide growth and development between successive hosts. Using data from 597 species of acanthocephalans, cestodes, and nematodes with two-host life cycles, we found that helminths with larger intermediate hosts were more likely to infect larger, endothermic definitive hosts, although some evolutionary shifts in definitive host mass occurred without changes in intermediate host mass. Life-history theory predicts parasites to shift growth to hosts in which they can grow rapidly and/or safely. Accordingly, helminth species grew relatively less as larvae and more as adults if they infected smaller intermediate hosts and/or larger, endothermic definitive hosts. Growing larger than expected in one host, relative to host mass/endothermy, was not associated with growing less in the other host, implying a lack of cross-host trade-offs. Rather, some helminth orders had both large larvae and large adults. Within these taxa, however, size at maturity in the definitive host was unaffected by changes to larval growth, as predicted by optimality models. Parasite life-history strategies were mostly (though not entirely) consistent with theoretical expectations, suggesting that helminths adaptively divide growth and development between the multiple hosts in their complex life cycles.

Quantitative kinetic modelling and mapping of cerebral glucose transport and metabolism using glucoCESL MRI.

Chemical-exchange spin-lock (CESL) MRI can map regional uptake and utilisation of glucose in the brain at high spatial resolution (i.e sub 0.2 mm3 voxels). We propose two quantitative kinetic models to describe glucose-induced changes in tissue R1ρ and apply them to glucoCESL MRI data acquired in tumour-bearing and healthy rats. When assuming glucose transport is saturable, the maximal transport capacity (Tmax) measured in normal tissue was 3.2 ± 0.6 µmol/min/mL, the half saturation constant (Kt) was 8.8 ± 2.2 mM, the metabolic rate of glucose consumption (MRglc) was 0.21 ± 0.13 µmol/min/mL, and the cerebral blood volume (vb) was 0.006 ± 0.005 mL/mL. Values in tumour were: Tmax = 7.1 ± 2.7 µmol/min/mL, Kt = 14 ± 1.7 mM, MRglc = 0.22 ± 0.09 µmol/min/mL, vb = 0.030 ± 0.035 mL/mL. Tmax and Kt were significantly higher in tumour tissue than normal tissue (p = 0.006 and p = 0.011, respectively). When assuming glucose uptake also occurs via free diffusion, the free diffusion rate (kd) was 0.061 ± 0.017 mL/min/mL in normal tissue and 0.12 ± 0.042 mL/min/mL in tumour. These parameter estimates agree well with literature values obtained using other approaches (e.g. NMR spectroscopy).