Neil P. Jerome

Comparison of free-breathing with navigator-controlled acquisition regimes in abdominal diffusion-weighted magnetic resonance images: Effect on ADC and IVIM statistics.

To evaluate the effect on diffusion‐weighted image‐derived parameters in the apparent diffusion coefficient (ADC) and intra‐voxel incoherent motion (IVIM) models from choice of either free‐breathing or navigator‐controlled acquisition.

Extended T2-IVIM model for correction of TE dependence of pseudo-diffusion volume fraction in clinical diffusion-weighted magnetic resonance imaging

Abstract The bi-exponential intravoxel-incoherent-motion (IVIM) model for diffusion-weighted MRI (DWI) fails to account for differential T2s in the model compartments, resulting in overestimation of pseudodiffusion fraction f. An extended model, T2-IVIM, allows removal of the confounding echo-time (TE) dependence of f, and provides direct compartment T2 estimates. Two consented healthy volunteer cohorts (n  =  5, 6) underwent DWI comprising multiple TE/b-value combinations (Protocol 1: TE  =  62–102 ms, b  =  0–250 mm−2s, 30 combinations. Protocol 2: 8 b-values 0–800 mm−2s at TE  =  62 ms, with 3 additional b-values 0–50 mm−2s at TE  =  80, 100 ms; scanned twice). Data from liver ROIs were fitted with IVIM at individual TEs, and with the T2-IVIM model using all data. Repeat-measures coefficients of variation were assessed for Protocol 2. Conventional IVIM modelling at individual TEs (Protocol 1) demonstrated apparent f increasing with longer TE: 22.4  ±  7% (TE  =  62 ms) to 30.7  ±  11% (TE  =  102 ms); T2-IVIM model fitting accounted for all data variation. Fitting of Protocol 2 data using T2-IVIM yielded reduced f estimates (IVIM: 27.9  ±  6%, T2-IVIM: 18.3  ±  7%), as well as T2  =  42.1  ±  7 ms, 77.6  ±  30 ms for true and pseudodiffusion compartments, respectively. A reduced Protocol 2 dataset yielded comparable results in a clinical time frame (11 min). The confounding dependence of IVIM f on TE can be accounted for using additional b/TE images and the extended T2-IVIM model.

Development of a temperature‐controlled phantom for magnetic resonance quality assurance of diffusion, dynamic, and relaxometry measurements

PURPOSE Diffusion-weighted (DW) and dynamic contrast-enhanced magnetic resonance imaging (MRI) are increasingly applied for the assessment of functional tissue biomarkers for diagnosis, lesion characterization, or for monitoring of treatment response. However, these techniques are vulnerable to the influence of various factors, so there is a necessity for a standardized MR quality assurance procedure utilizing a phantom to facilitate the reliable estimation of repeatability of these quantitative biomarkers arising from technical factors (e.g., B1 variation) affecting acquisition on scanners of different vendors and field strengths. The purpose of this study is to present a novel phantom designed for use in quality assurance for multicenter trials, and the associated repeatability measurements of functional and quantitative imaging protocols across different MR vendors and field strengths. METHODS A cylindrical acrylic phantom was manufactured containing 7 vials of polyvinylpyrrolidone (PVP) solutions of different concentrations, ranging from 0% (distilled water) to 25% w/w, to create a range of different MR contrast parameters. Temperature control was achieved by equilibration with ice-water. Repeated MR imaging measurements of the phantom were performed on four clinical scanners (two at 1.5 T, two at 3.0 T; two vendors) using the same scanning protocol to assess the long-term and short-term repeatability. The scanning protocol consisted of DW measurements, inversion recovery (IR) T1 measurements, multiecho T2 measurement, and dynamic T1-weighted sequence allowing multiple variable flip angle (VFA) estimation of T1 values over time. For each measurement, the corresponding calculated parameter maps were produced. On each calculated map, regions of interest (ROIs) were drawn within each vial and the median value of these voxels was assessed. For the dynamic data, the autocorrelation function and their variance were calculated; for the assessment of the repeatability, the coefficients of variation (CoV) were calculated. RESULTS For both field strengths across the available vendors, the apparent diffusion coefficient (ADC) at 0 °C ranged from (1.12 ± 0.01) × 10(-3) mm(2)/s for pure water to (0.48 ± 0.02) × 10(-3) mm(2)/s for the 25% w/w PVP concentration, presenting a minor variability between the vendors and the field strengths. T2 and IR-T1 relaxation time results demonstrated variability between the field strengths and the vendors across the different acquisitions. Moreover, the T1 values derived from the VFA method exhibited a large variation compared with the IR-T1 values across all the scanners for all repeated measurements, although the calculation of the standard deviation of the VFA-T1 estimate across each ROI and the autocorrelation showed a stability of the signal for three scanners, with autocorrelation of the signal over the dynamic series revealing a periodic variation in one scanner. Finally, the ADC, the T2, and the IR-T1 values exhibited an excellent repeatability across the scanners, whereas for the dynamic data, the CoVs were higher. CONCLUSIONS The combination of a novel PVP phantom, with multiple compartments to give a physiologically relevant range of ADC and T1 values, together with ice-water as a temperature-controlled medium, allows reliable quality assurance measurements that can be used to measure agreement between MRI scanners, critical in multicenter functional and quantitative imaging studies.

Extracranial Soft-Tissue Tumors: Repeatability of Apparent Diffusion Coefficient Estimates from Diffusion-weighted MR Imaging

Purpose To assess the repeatability of apparent diffusion coefficient (ADC) estimates in extracranial soft-tissue diffusion-weighted magnetic resonance imaging across a wide range of imaging protocols and patient populations. Materials and Methods Nine prospective patient studies and one prospective volunteer study, performed between 2006 and 2016 with research ethics committee approval and written informed consent from each subject, were included in this single-institution study. A total of 141 tumors and healthy organs were imaged twice (interval between repeated examinations, 45 minutes to 10 days, depending the on study) to assess the repeatability of median and mean ADC estimates. The Levene test was used to determine whether ADC repeatability differed between studies. The Pearson linear correlation coefficient was used to assess correlation between coefficient of variation (CoV) and the year the study started, study size, and volumes of tumors and healthy organs. The repeatability of ADC estimates from small, medium, and large tumors and healthy organs was assessed irrespective of study, and the Levene test was used to determine whether ADC repeatability differed between these groups. Results CoV aggregated across all studies was 4.1% (range for each study, 1.7%-6.5%). No correlation was observed between CoV and the year the study started or study size. CoV was weakly correlated with volume (r = -0.5, P = .1). Repeatability was significantly different between small, medium, and large tumors (P < .05), with the lowest CoV (2.6%) for large tumors. There was a significant difference in repeatability between studies-a difference that did not persist after the study with the largest tumors was excluded. Conclusion ADC is a robust imaging metric with excellent repeatability in extracranial soft tissues across a wide range of tumor sites, sizes, patient populations, and imaging protocol variations. Online supplemental material is available for this article.

Use of the temporal median and trimmed mean mitigates effects of respiratory motion in multiple-acquisition abdominal diffusion imaging.

Respiratory motion commonly confounds abdominal diffusion-weighted magnetic resonance imaging, where averaging of successive samples at different parts of the respiratory cycle, performed in the scanner, manifests the motion as blurring of tissue boundaries and structural features and can introduce bias into calculated diffusion metrics. Storing multiple averages separately allows processing using metrics other than the mean; in this prospective volunteer study, median and trimmed mean values of signal intensity for each voxel over repeated averages and diffusion-weighting directions are shown to give images with sharper tissue boundaries and structural features for moving tissues, while not compromising non-moving structures. Expert visual scoring of derived diffusion maps is significantly higher for the median than for the mean, with modest improvement from the trimmed mean. Diffusion metrics derived from mono- and bi-exponential diffusion models are comparable for non-moving structures, demonstrating a lack of introduced bias from using the median. The use of the median is a simple and computationally inexpensive alternative to complex and expensive registration algorithms, requiring only additional data storage (and no additional scanning time) while returning visually superior images that will facilitate the appropriate placement of regions-of-interest when analysing abdominal diffusion-weighted magnetic resonance images, for assessment of disease characteristics and treatment response.

T2-adjusted computed diffusion-weighted imaging

PURPOSE To introduce T2-adjusted computed DWI (T2-cDWI), a method that provides synthetic images at arbitrary b-values and echo times (TEs) that improve tissue contrast by removing or increasing T2 contrast in diffusion-weighted images. MATERIALS AND METHODS In addition to the standard DWI acquisition protocol T2-weighted echo-planar images at multiple (≥2) echo times were acquired. This allows voxelwise estimation of apparent diffusion coefficient (ADC) and T2 values, permitting synthetic images to be generated at any chosen b-value and echo time. An analytical model is derived for the noise properties in T2-cDWI, and validated using a diffusion test-object. Furthermore, we present T2-cDWI in two example clinical case studies: (i) a patient with mesothelioma demonstrating multiple disease tissue compartments and (ii) a patient with primary ovarian cancer demonstrating solid and cystic disease compartments. RESULTS Measured image noise in T2-cDWI from phantom experiments conformed to the analytical model and demonstrated that T2-cDWI at high computed b-value/TE combinations achieves lower noise compared with conventional DWI. In patients, T2-cDWI with low b-value and long TE enhanced fluid signal while suppressing solid tumour components. Conversely, large b-values and short TEs overcome T2 shine-through effects and increase the contrast between tumour and fluid compared with conventional high-b-value DW images. CONCLUSION T2-cDWI is a promising clinical tool for improving image signal-to-noise, image contrast, and tumour detection through suppression of T2 shine-through effects.

Characterisation of fibrosis in chemically-induced rat mammary carcinomas using multi-modal endogenous contrast MRI on a 1.5T clinical platform

ObjectivesTo determine the ability of multi-parametric, endogenous contrast MRI to detect and quantify fibrosis in a chemically-induced rat model of mammary carcinoma.MethodsFemale Sprague-Dawley rats (n=18) were administered with N-methyl-N-nitrosourea; resulting mammary carcinomas underwent nine-b-value diffusion-weighted (DWI), ultrashort-echo (UTE) and magnetisation transfer (MT) magnetic resonance imaging (MRI) on a clinical 1.5T platform, and associated quantitative MR parameters were calculated. Excised tumours were histologically assessed for degree of necrosis, collagen, hypoxia and microvessel density. Significance level adjusted for multiple comparisons was p=0.0125.ResultsSignificant correlations were found between MT parameters and degree of picrosirius red staining (r > 0.85, p < 0.0002 for ka and δ, r < -0.75, p < 0.001 for T1 and T1s, Pearson), indicating that MT is sensitive to collagen content in mammary carcinoma. Picrosirius red also correlated with the DWI parameter fD* (r=0.801, p=0.0004) and conventional gradient-echo T2* (r=-0.660, p=0.0055). Percentage necrosis correlated moderately with ultrashort/conventional-echo signal ratio (r=0.620, p=0.0105). Pimonidazole adduct (hypoxia) and CD31 (microvessel density) staining did not correlate with any MR parameter assessed.ConclusionsMagnetisation transfer MRI successfully detects collagen content in mammary carcinoma, supporting inclusion of MT imaging to identify fibrosis, a prognostic marker, in clinical breast MRI examinations.Key Points• Magnetisation transfer imaging is sensitive to collagen content in mammary carcinoma.• Magnetisation transfer imaging to detect fibrosis in mammary carcinoma fibrosis is feasible.• IVIM diffusion does not correlate with microvessel density in preclinical mammary carcinoma.

Feasibility and applicability of diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging in routine assessments of children with high-grade gliomas

Diffusion‐weighted (DW) and dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) have been used as imaging biomarkers in adults with high‐grade gliomas (HGGs). We incorporated free‐breathing DW‐MRI and DCE‐MRI, at a single time point, in the routine follow‐up of five children (median age 9 years, range 8–15) with histologically confirmed HGG within a prospective imaging study. It was feasible to incorporate DW‐MRI and DCE‐MRI in routine assessments of children with HGG. DW and DCE parameters were repeatable in paediatric HGG. Higher median ADC100‐1000 significantly correlated with longer survival in our sample.