Magnetic Resonance Diffusion Weighted Imaging: Flow Compensated Intravoxel Incoherent Motion Imaging as a Tool to Probe Microvasculature

Flow compensated and monopolar diffusion weighting gradients are employed to determine the characteristic time scale of the incoherent blood motion causing the biexponential signal decay. A pulse sequence for diffusion weighted magnetic resonance imaging is developed, which allows one to suppress velocity encoding of imaging gradients and which is designed such that the influence of concomitant fields is reduced. It is tested with phantoms and healthy volunteers, revealing different signal attenuation curves for flow compensated and monopolar diffusion gradients in liver and pancreas. Furthermore, a dependence on the total duration of the applied diffusion gradient profile is measured. To describe the experimentally observed signal attenuation curves, a model is developed, which allows one to calculate the signal attenuation due to incoherent blood motion for arbitrary diffusion gradient profiles. Precalculated normalized phase distributions allow one to fit the model to the experimental data. For the signal attenuation curves averaged over test subjects, the characteristic timescale of the blood motion is found to be τ = 184±64 ms in pancreas and τ = 156 ± 22 ms in liver. To facilitate a pixel-wise evaluation and the creation of parameter maps, a denoising algorithm based on principal component analysis is implemented. The denoising reduces the effect of pseudo-random signal contributions allowing one to obtain parameter maps from only 33% of the originally acquired data, which are less affected by noise than the original ones

Texture analysis using proton density and T2 relaxation in patients with histological usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP)

Objectives The purpose of our study was to assess proton density (PD) and T2 relaxation time of usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP) and to evaluate their utility in differentiating the two patterns. Furthermore, we aim to investigate whether these two parameters could help differentiate active-inflammatory and stable-fibrotic lesions in NSIP. Methods 32 patients (mean age: 69 years;M:F, 1: 1) with pathologically proven disease (UIP: NSIP, 1: 1), underwent thoracic thin-section multislice CT scan and 1.5T MRI. A total of 437 regions-of-interest (ROIs) were classified at CT as advanced, moderate or mild alterations. Based on multi-echo single-shot TSE sequence acquired at five echo times, with breath-holding at end-expiration and ECG-triggering, entire lung T2 and PD maps were generated from each subject. The T2 relaxation time and the respective signal intensity were quantified by performing a ROI measurement on the T2 and PD maps in the corresponding CT selected areas of the lung. Results UIP and NSIP regional patterns could not be differentiated by T2 relaxation times or PD values alone. Overall, a strong positive correlation was found between T2 relaxation and PD in NSIP, r = 0.64, p0.05. Conclusions T2 relaxation times and PD values may provide helpful quantitative information for differentiating NSIP from UIP pattern. These parameters have the potential to differentiate active-inflammatory and stable-fibrotic lesions in NSIP

Recommendations for improved reproducibility of ADC derivation on behalf of the Elekta MRI-linac consortium image analysis working group

Background and purpose: The apparent diffusion coefficient (ADC), a potential imaging biomarker for radiotherapy response, needs to be reproducible before translation into clinical use. The aim of this study was to evaluate the multi-centre delineation- and calculation-related ADC variation and give recommendations to minimize it. Materials and methods: Nine centres received identical diffusion-weighted and anatomical magnetic resonance images of different cancerous tumours (adrenal gland, pelvic oligo metastasis, pancreas, and prostate). All centres delineated the gross tumour volume (GTV), clinical target volume (CTV), and viable tumour volume (VTV), and calculated ADCs using both their local calculation methods and each of the following calculation conditions: b-values 0–500 vs. 150–500 s/mm 2, region-of-interest (ROI)-based vs. voxel-based calculation, and mean vs. median. ADC variation was assessed using the mean coefficient of variation across delineations (CV D) and calculation methods (CV C). Absolute ADC differences between calculation conditions were evaluated using Friedman's test. Recommendations for ADC calculation were formulated based on observations and discussions within the Elekta MRI-linac consortium image analysis working group. Results: The median (range) CV D and CV C were 0.06 (0.02–0.32) and 0.17 (0.08–0.26), respectively. The ADC estimates differed 18% between b-value sets and 4% between ROI/voxel-based calculation (p-values < 0.01). No significant difference was observed between mean and median (p = 0.64). Aligning calculation conditions between centres reduced CV C to 0.04 (0.01–0.16). CV D was comparable between ROI types. Conclusion: Overall, calculation methods had a larger impact on ADC reproducibility compared to delineation. Based on the results, significant sources of variation were identified, which should be considered when initiating new studies, in particular multi-centre investigations

Accelerating 4D image reconstruction for magnetic resonance-guided radiotherapy

Background and purpose: Physiological motion impacts the dose delivered to tumours and vital organs in external beam radiotherapy and particularly in particle therapy. The excellent soft-tissue demarcation of 4D magnetic resonance imaging (4D-MRI) could inform on intra-fractional motion, but long image reconstruction times hinder its use in online treatment adaptation. Here we employ techniques from high-performance computing to reduce 4D-MRI reconstruction times below two minutes to facilitate their use in MR-guided radiotherapy. Material and methods: Four patients with pancreatic adenocarcinoma were scanned with a radial stack-of-stars gradient echo sequence on a 1.5T MR-Linac. Fast parallelised open-source implementations of the extra-dimensional golden-angle radial sparse parallel algorithm were developed for central processing unit (CPU) and graphics processing unit (GPU) architectures. We assessed the impact of architecture, oversampling and respiratory binning strategy on 4D-MRI reconstruction time and compared images using the structural similarity (SSIM) index against a MATLAB reference implementation. Scaling and bottlenecks for the different architectures were studied using multi-GPU systems. Results: All reconstructed 4D-MRI were identical to the reference implementation (SSIM > 0.99). Images reconstructed with overlapping respiratory bins were sharper at the cost of longer reconstruction times. The CPU  + GPU implementation was over 17 times faster than the reference implementation, reconstructing images in 60 ± 1 s and hyper-scaled using multiple GPUs. Conclusion: Respiratory-resolved 4D-MRI reconstruction times can be reduced using high-performance computing methods for online workflows in MR-guided radiotherapy with potential applications in particle therapy

Incidental coronary artery calcification on non-gated CT thorax correlates with risk of cardiovascular events and death.

OBJECTIVES: To assess coronary artery calcification (CAC) on non-contrast non-ECG-gated CT thorax (NC-NECG-CTT) and to evaluate its correlation with short-term risk of cardiovascular disease (CVD) events and death. METHODS: Single-institution retrospective study including all patients 40-70 years old who underwent NC-NECG-CTT over a period of 6 months. Individuals with known CVD were excluded. The presence of CAC was assessed and quantified by the Agatston score (CACS). CAC severity was defined as mild ( 400). CVD events (including CVD death, myocardial infarction, revascularisation procedures, ischaemic stroke, acute peripheral atherosclerotic ischaemia), and all-cause mortality over a median of 3.5 years were recorded. Cox proportional-hazards regression modelling was performed including CACS, age, gender and CVD risk factors (smoking, hypertension, diabetes mellitus, dyslipidaemia, and family history of CVD). RESULTS: Of the total 717 eligible cases, 325 (45%) had CAC. In patients without CAC, there was only one CVD event, compared to 26 CVD events including 5 deaths in patients with CAC. The presence and severity of CAC correlated with CVD events (p  100 was significantly associated with both CVD events, hazard ratio (HR) 5.74, 95% confidence interval: 2.19-15.02; p < 0.001, and all-cause mortality, HR 1.7, 95% CI: 1.08-2.66; p = 0.02. Ever-smokers with CAC had a significantly higher risk for all-cause mortality compared to never-smokers (p = 0.03), but smoking status was not an independent predictor for CVD events in any subgroup category of CAC severity. CONCLUSIONS: The presence and severity of CAC assessed on NC-NECG-CTT correlates with short-term cardiovascular events and death. KEY POINTS: • Patients aged 40-70 years old without known CVD but with CAC on NC-NECG-CTT have a higher risk of CVD events compared to those without CAC. • CAC (Agatston) score above 100 confers a 5.7-fold increase in the risk of short-term CVD events in these patients. • The presence and severity of CAC on NC-NECG-CTT may have prognostic and therapeutic implications

Echo time dependence of biexponential and triexponential intravoxel incoherent motion parameters in the liver

Purpose: Intravoxel incoherent motion (IVIM) studies are performed with different acquisition protocols. Comparing them requires knowledge of echo time (TE) dependencies. The TE-dependence of the biexponential perfusion fraction f is well-documented, unlike that of its triexponential counterparts f1 and f2 and the biexponential and triexponential pseudodiffusion coefficients D*, (Formula presented.), and (Formula presented.). The purpose was to investigate the TE-dependence of these parameters and to check whether the triexponential pseudodiffusion compartments are associated with arterial and venous blood. Methods: Fifteen healthy volunteers (19-58 y; mean: 24.7 y) underwent diffusion-weighted imaging of the abdomen with 24 b-values (0.2-800 s/mm2) at TEs of 45, 60, 75, and 90 ms. Regions of interest (ROIs) were manually drawn in the liver. One set of bi- and triexponential IVIM parameters per volunteer and TE was determined. The TE-dependence was assessed with the Kruskal-Wallis test. Results: TE-dependence was observed for f (P <.001), f1 (P =.001), and f2 (P <.001). Their median values at the four measured TEs were: f: 0.198/0.240/0.274/0.359, f1: 0.113/0.139/0.146/0.205, f2: 0.115/0.155/0.182/0.194. D, D*, (Formula presented.), and (Formula presented.) showed no significant TE-dependence. Their values were: diffusion coefficient D (10−4 mm2/s): 9.45/9.63/9.75/9.41, biexponential D* (10−2 mm2/s): 5.26/5.52/6.13/5.82, triexponential (Formula presented.) (10−2 mm2/s): 1.73/2.91/2.25/2.51, triexponential (Formula presented.) (mm2/s): 0.478/1.385/0.616/0.846. Conclusion: f1 and f2 show similar TE-dependence as f, ie, increase with rising TE; an effect that must be accounted for when comparing different studies. The diffusion and pseudodiffusion coefficients might be compared without TE correction. Because of the similar TE-dependence of f1 and f2, the triexponential pseudodiffusion compartments are most probably not associated to venous and arterial blood

Respiratory motion modelling for MR-guided lung cancer radiotherapy: model development and geometric accuracy evaluation.

Funder: NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research; doi: https://doi.org/10.13039/100014461Objective.Respiratory motion of lung tumours and adjacent structures is challenging for radiotherapy. Online MR-imaging cannot currently provide real-time volumetric information of the moving patient anatomy, therefore limiting precise dose delivery, delivered dose reconstruction, and downstream adaptation methods.Approach.We tailor a respiratory motion modelling framework towards an MR-Linac workflow to estimate the time-resolved 4D motion from real-time data. We develop a multi-slice acquisition scheme which acquires thick, overlapping 2D motion-slices in different locations and orientations, interleaved with 2D surrogate-slices from a fixed location. The framework fits a motion model directly to the input data without the need for sorting or binning to account for inter- and intra-cycle variation of the breathing motion. The framework alternates between model fitting and motion-compensated super-resolution image reconstruction to recover a high-quality motion-free image and a motion model. The fitted model can then estimate the 4D motion from 2D surrogate-slices. The framework is applied to four simulated anthropomorphic datasets and evaluated against known ground truth anatomy and motion. Clinical applicability is demonstrated by applying our framework to eight datasets acquired on an MR-Linac from four lung cancer patients.Main results.The framework accurately reconstructs high-quality motion-compensated 3D images with 2 mm3isotropic voxels. For the simulated case with the largest target motion, the motion model achieved a mean deformation field error of 1.13 mm. For the patient cases residual error registrations estimate the model error to be 1.07 mm (1.64 mm), 0.91 mm (1.32 mm), and 0.88 mm (1.33 mm) in superior-inferior, anterior-posterior, and left-right directions respectively for the building (application) data.Significance.The motion modelling framework estimates the patient motion with high accuracy and accurately reconstructs the anatomy. The image acquisition scheme can be flexibly integrated into an MR-Linac workflow whilst maintaining the capability of online motion-management strategies based on cine imaging such as target tracking and/or gating

On the Field Strength Dependence of Bi- and Triexponential Intravoxel Incoherent Motion (IVIM) Parameters in the Liver

Background: Studies on intravoxel incoherent motion (IVIM) imaging are carried out with different acquisition protocols. Purpose: To investigate the dependence of IVIM parameters on the B0 field strength when using a bi- or triexponential model. Study Type: Prospective. Study Population: 20 healthy volunteers (age: 19–28 years). Field Strength/Sequence: Volunteers were examined at two field strengths (1.5 and 3T). Diffusion-weighted images of the abdomen were acquired at 24 b-values ranging from 0.2 to 500 s/mm2. Assessment: ROIs were manually drawn in the liver. Data were fitted with a bi- and a triexponential IVIM model. The resulting parameters were compared between both field strengths. Statistical Tests: One-way analysis of variance (ANOVA) and Kruskal–Wallis test were used to test the obtained IVIM parameters for a significant field strength dependency. Results: At b-values below 6 s/mm2, the triexponential model provided better agreement with the data than the biexponential model. The average tissue diffusivity was D = 1.22/1.00 μm2/msec at 1.5/3T. The average pseudodiffusion coefficients for the biexponential model were D* = 308/260 μm2/msec at 1.5/3T; and for the triexponential model D* = 81.3/65.9 μm2/msec, D* 2 = 2453/2333 μm2/msec at 1.5/3T. The average perfusion fractions for the biexponential model were f = 0.286/0.303 at 1.5/3T; and for the triexponential model f1 = 0.161/0.174 and f2 = 0.152/0.159 at 1.5/3T. A significant B0 dependence was only found for the biexponential pseudodiffusion coefficient (ANOVA/KW P = 0.037/0.0453) and tissue diffusivity (ANOVA/KW: P < 0.001). Data Conclusion: Our experimental results suggest that triexponential pseudodiffusion coefficients and perfusion fractions obtained at different field strengths could be compared across different studies using different B0. However, it is recommended to take the field strength into account when comparing tissue diffusivities or using the biexponential IVIM model. Considering published values for oxygenation-dependent transversal relaxation times of blood, it is unlikely that the two blood compartments of the triexponential model represent venous and arterial blood. Level of Evidence: 1. Technical Efficacy Stage: 2. J. Magn. Reson. Imaging 2019;50:1883–1892

On the field strength dependence of Bi- and Triexponential Intravoxel Incoherent Motion (IVIM) parameters in the liver

Background Studies on intravoxel incoherent motion (IVIM) imaging are carried out with different acquisition protocols. Purpose To investigate the dependence of IVIM parameters on the B0 field strength when using a bi‐ or triexponential model. Study Type Prospective. Study Population 20 healthy volunteers (age: 19–28 years). Field Strength/Sequence Volunteers were examined at two field strengths (1.5 and 3T). Diffusion‐weighted images of the abdomen were acquired at 24 b‐values ranging from 0.2 to 500 s/mm2. Assessment ROIs were manually drawn in the liver. Data were fitted with a bi‐ and a triexponential IVIM model. The resulting parameters were compared between both field strengths. Statistical Tests One‐way analysis of variance (ANOVA) and Kruskal–Wallis test were used to test the obtained IVIM parameters for a significant field strength dependency. Results At b‐values below 6 s/mm2, the triexponential model provided better agreement with the data than the biexponential model. The average tissue diffusivity was D = 1.22/1.00 μm2/msec at 1.5/3T. The average pseudodiffusion coefficients for the biexponential model were D* = 308/260 μm2/msec at 1.5/3T; and for the triexponential model urn:x-wiley:10531807:media:jmri26730:jmri26730-math-0001 = 81.3/65.9 μm2/msec, urn:x-wiley:10531807:media:jmri26730:jmri26730-math-0002 = 2453/2333 μm2/msec at 1.5/3T. The average perfusion fractions for the biexponential model were f = 0.286/0.303 at 1.5/3T; and for the triexponential model f1 = 0.161/0.174 and f2 = 0.152/0.159 at 1.5/3T. A significant B0 dependence was only found for the biexponential pseudodiffusion coefficient (ANOVA/KW P = 0.037/0.0453) and tissue diffusivity (ANOVA/KW: P < 0.001). Data Conclusion Our experimental results suggest that triexponential pseudodiffusion coefficients and perfusion fractions obtained at different field strengths could be compared across different studies using different B0. However, it is recommended to take the field strength into account when comparing tissue diffusivities or using the biexponential IVIM model. Considering published values for oxygenation‐dependent transversal relaxation times of blood, it is unlikely that the two blood compartments of the triexponential model represent venous and arterial blood