MR Sequence Development for Imaging Venous Blood Flow in the Leg

Deep Vein Thrombosis is a common complication in bed-ridden patients, described as the main cause of preventable hospital deaths in the UK (NICE 2010). Mechanical prophylaxis aims to promote venous flow, either statically with compression stockings, or dynamically with intermittent pneumatic compression or electrical muscle stimulation. Previous studies used ultrasound for venous flow measurements, limited to a single deep vein at a time, and some anatomical MRI for investigating the mechanisms behind these prophylaxes. MRI velocity mapping is used clinically in the arterial system where gating enables data accumulation over multiple cardiac cycles. This thesis describes the development of two real-time MRI spiral velocity mapping sequences for imaging venous blood flow in the leg, where venous flow variability is largely unrelated to the cardiac cycle. Real-time imaging with spiral gradient readouts minimised image duration. A phase-image fitting technique requiring only a velocity-encoded phase image was implemented for acceleration. For in vivo comparison, conventional flow imaging required metronome-guided breathing for a regular venous flow waveform. The long spiral readouts were sensitive to off-resonance and flow artefacts, where some unpublished effects were investigated. The off-resonance associated with deoxygenation of venous blood did not cause notable spiral artefacts, but disrupted the phase-image fitting technique and required correction with a pre-scan. The spiral flow methods demonstrated increased venous blood velocity and flow during application of mechanical compression. Metronome-guided breathing was also applied to vein wall imaging, where it detected wall thickening in patients with Behçet’s disease compared with normal subjects. For the first time, this thesis evaluated real-time MRI spiral velocity mapping of venous blood velocity and flow. The high resolution (1mm) and short image time required caused challenging off-resonance and flow artefacts. With some limitations, real-time spiral flow MRI during operation of compression devices may assist in their optimisation

Myocardial Approximate Spin-lock Dispersion Mapping using a Simultaneous T2 and TRAFF2 Mapping at 3T MRI

Ischemic heart disease (IHD) is one of the leading causes of death worldwide. Myocardial infarction (MI) represents a third of all IHD cases, and cardiac magnetic resonance imaging (MRI) is often used to assess its damage to myocardial viability. Late gadolinium enhancement (LGE) is the current gold standard, but the use of gadolinium-based agents limits the clinical applicability in some patients. Spin-lock (SL) dispersion has recently been proposed as a promising non-contrast biomarker for the assessment of MI. However, at 3T, the required range of SL preparations acquired at different amplitudes suffers from specific absorption rate (SAR) limitations and off-resonance artifacts. Relaxation Along a Fictitious Field (RAFF) is an alternative to SL preparations with lower SAR requirements, while still sampling relaxation in the rotating frame. In this study, a single breath-hold simultaneous TRAFF2 and T2 mapping sequence is proposed for SL dispersion mapping at 3T. Excellent reproducibility (coefficient of variations lower than 10%) was achieved in phantom experiments, indicating good intrascan repeatability. The average myocardial TRAFF2, T2, and SL dispersion obtained with the proposed sequence (68.0±10.7 ms, 44.0±4.0 ms, and 0.4±0.2 ×10-4 s2, respectively) were comparable to the reference methods (62.7±11.7 ms, 41.2±2.4 ms, and 0.3±0.2x 10-4s2, respectively). High visual map quality, free of B0 and B1+ related artifacts, for T2, TRAFF2, and SL dispersion maps were obtained in phantoms and in vivo, suggesting promise in clinical use at 3T. Clinical relevance - and imaging promises non-contrast assessment of scar and focal fibrosis in a single breath-hold using approximate spin-lock dispersion mapping

Improved reproducibility for myocardial ASL: Impact of physiological and acquisition parameters

PURPOSE: To investigate and mitigate the influence of physiological and acquisition-related parameters on myocardial blood flow (MBF) measurements obtained with myocardial Arterial Spin Labeling (myoASL). METHODS: A Flow-sensitive Alternating Inversion Recovery (FAIR) myoASL sequence with bSSFP and spoiled GRE (spGRE) readout is investigated for MBF quantification. Bloch-equation simulations and phantom experiments were performed to evaluate how variations in acquisition flip angle (FA), acquisition matrix size (AMS), heart rate (HR) and blood T 1 $${\mathrm{T}}_1$$ relaxation time ( T 1 , B $${\mathrm{T}}_{1,B}$$ ) affect quantification of myoASL-MBF. In vivo myoASL-images were acquired in nine healthy subjects. A corrected MBF quantification approach was proposed based on subject-specific T 1 , B $${\mathrm{T}}_{1,B}$$ values and, for spGRE imaging, subtracting an additional saturation-prepared baseline from the original baseline signal. RESULTS: Simulated and phantom experiments showed a strong dependence on AMS and FA ( R 2 $${R}^2$$ >0.73), which was eliminated in simulations and alleviated in phantom experiments using the proposed saturation-baseline correction in spGRE. Only a very mild HR dependence ( R 2 $${R}^2$$ >0.59) was observed which was reduced when calculating MBF with individual T 1 , B $${\mathrm{T}}_{1,B}$$ . For corrected spGRE, in vivo mean global spGRE-MBF ranged from 0.54 to 2.59 mL/g/min and was in agreement with previously reported values. Compared to uncorrected spGRE, the intra-subject variability within a measurement (0.60 mL/g/min), between measurements (0.45 mL/g/min), as well as the inter-subject variability (1.29 mL/g/min) were improved by up to 40% and were comparable with conventional bSSFP. CONCLUSION: Our results show that physiological and acquisition-related factors can lead to spurious changes in myoASL-MBF if not accounted for. Using individual T 1 , B $${\mathrm{T}}_{1,B}$$ and a saturation-baseline can reduce these variations in spGRE and improve reproducibility of FAIR-myoASL against acquisition parameters

A Global Assessment of Gold, Titanium, Strontium and Barium Pollution Using Sperm Whales (Physeter Macrocephalus) As an Indicator Species

This study provides a global baseline for barium, gold, titanium and strontium as marine pollutants using the sperm whale (Physeter macrocephalus) as an indicator species. Barium, gold, titanium and strontium are metals that are little studied in marine environments. However, their recent emergence as nanomaterials will likely increase their presence in the marine environment. Moreover, nanosized particles are likely to exhibit toxic outcomes not seen in macrosized particles. Biopsies from free ranging sperm whales were collected from around the globe. Total barium levels were measured in 275 of 298 sperm whales tested for barium and collected from 16 regions around the globe. The global mean for barium was 0.93 +/- 0.2ug/g with a detectable range from 0.1 to 27.9ug. Total strontium levels were measurable in all 298 sperm whales producing a global mean level of 2.2 +/- 0.1ug/g and a range from 0.2 to 11.5ug/g. Total titanium levels were also measured in all 298 sperm whales producing a global mean level of 4.5 +/- 0.25ug/g with a range from 0.1 to 29.8ug/g. Total gold levels were detected in 50 of the 194 sperm whales collected from 16 regions around the globe. Detectable levels ranged from 0.1 to 2.3ug/g tissue with a global mean level equal to 0.2 +/- 0.02ug/g. Previous reports of these metals were much lower than the mean levels reported here. The likely explanation is location differences and consistent with this explanation, we found statistically significant variation among regions. These data provide an important global baseline for barium, gold, titanium and strontium pollution and will allow for important comparisons to be made over time to assess the impact of nanomaterials on whales and the marine environment

Updates to the Integrated Protein–Protein Interaction Benchmarks: Docking Benchmark Version 5 and Affinity Benchmark Version 2

We present an updated and integrated version of our widely used protein–protein docking and binding affinity benchmarks. The benchmarks consist of non-redundant, high-quality structures of protein–protein complexes along with the unbound structures of their components. Fifty-five new complexes were added to the docking benchmark, 35 of which have experimentally measured binding affinities. These updated docking and affinity benchmarks now contain 230 and 179 entries, respectively. In particular, the number of antibody–antigen complexes has increased significantly, by 67% and 74% in the docking and affinity benchmarks, respectively. We tested previously developed docking and affinity prediction algorithms on the new cases. Considering only the top 10 docking predictions per benchmark case, a prediction accuracy of 38% is achieved on all 55 cases and up to 50% for the 32 rigid-body cases only. Predicted affinity scores are found to correlate with experimental binding energies up to r = 0.52 overall and r = 0.72 for the rigid complexes.Peer ReviewedPostprint (author's final draft

Incremental benefit in correlation with histology of native T1 mapping, partition coefficient and extracellular volume fraction in patients with aortic stenosis

Background: We investigated the histological correlation of native T1 maps, partition coefficient and extracellular volume fraction (ECV) using an 11 heart beat (11 HB) MOLLI for identification of overall burden of fibrosis. Methods: Ten patients (8 male, age 73 ± 7 years; all in sinus rhythm, 2 with ventricular ectopy) with severe aortic stenosis (3 with coexisting coronary artery disease) scheduled for surgical aortic valve replacement underwent CMR on a 1.5T scanner (MAGNETOM Avanto, Siemens Healthcare, Erlangen). The 11HB MOLLI sequence (Siemens investigational prototype WIP 448B) was acquired before and 15 minutes post 0.1 mmol/kg gadolinium administration. Incorporating hematocrit results from the same day. This allowed native T1 maps, partition coefficient and ECV calculation. Images were obtained twice at end diastole at basal, and twice at mid left ventricular level. The average of all measurements was used to calculate ECV using the standard formula Partition Coefficient= [(1/T1myocardium post contrast-1/T1 myocardium native)]/[(1/T1 blood post contrast-1/T1 blood native)] with x(1-HCt) for ECV. Similar regions of interest were drawn in the septum at both levels for T1 values. Intraoperatively, trucut biopsies were taken from the left ventricular apical anterior/ lateral wall through the epicardium to allow histological characterization of the full myocardial wall, and fixed in warm buffered formalin. Histological analysis of formalin-fixed paraffin-embedded, transmural myocardial biopsies of the left ventricle was performed on hematoxylin/eosin and Picrosirius red-stained 3-micron-thick sections by a blinded experienced cardiac pathologist. Images were analysed using a purpose-built software (Nikon NIS elements BR) on a NIKON Eclipse light projection microscope to determine the extent of overall and reactive interstitial fibrosis, which was expressed as collagen volume fraction (%) per square millimetre. Results: Native T1 mapping, partition coefficient and ECV all correlated with histologically measured fibrosis. However, native T1 mapping showed the least accuracy (panel A, R2 = 0.42) and ECV showed the highest accuracy (panel B, R2 = 0.83). Partition coefficient was more accurate than native T1 mapping but only very marginally less so than ECV (panel C, R2 = 0.80). Conclusions: These results suggest that native T1 mapping is less accurate than partition coefficient and ECV for overall fibrosis. Therefore, post gadolinium images to enable calculation of partition coefficient and ECV should be routinely obtained to increase accuracy

Developing a medical device-grade T2 phantom optimized for myocardial T2 mapping by cardiovascular magnetic resonance

INTRODUCTION: A long T2 relaxation time can reflect oedema, and myocardial inflammation when combined with increased plasma troponin levels. Cardiovascular magnetic resonance (CMR) T2 mapping therefore has potential to provide a key diagnostic and prognostic biomarkers. However, T2 varies by scanner, software, and sequence, highlighting the need for standardization and for a quality assurance system for T2 mapping in CMR. AIM: To fabricate and assess a phantom dedicated to the quality assurance of T2 mapping in CMR. METHOD: A T2 mapping phantom was manufactured to contain 9 T1 and T2 (T1|T2) tubes to mimic clinically relevant native and post-contrast T2 in myocardium across the health to inflammation spectrum (i.e., 43-74 ms) and across both field strengths (1.5 and 3 T). We evaluated the phantom's structural integrity, B0 and B1 uniformity using field maps, and temperature dependence. Baseline reference T1|T2 were measured using inversion recovery gradient echo and single-echo spin echo (SE) sequences respectively, both with long repetition times (10 s). Long-term reproducibility of T1|T2 was determined by repeated T1|T2 mapping of the phantom at baseline and at 12 months. RESULTS: The phantom embodies 9 internal agarose-containing T1|T2 tubes doped with nickel di-chloride (NiCl2) as the paramagnetic relaxation modifier to cover the clinically relevant spectrum of myocardial T2. The tubes are surrounded by an agarose-gel matrix which is doped with NiCl2 and packed with high-density polyethylene (HDPE) beads. All tubes at both field strengths, showed measurement errors up to ≤ 7.2 ms [< 14.7%] for estimated T2 by balanced steady-state free precession T2 mapping compared to reference SE T2 with the exception of the post-contrast tube of ultra-low T1 where the deviance was up to 16 ms [40.0%]. At 12 months, the phantom remained free of air bubbles, susceptibility, and off-resonance artifacts. The inclusion of HDPE beads effectively flattened the B0 and B1 magnetic fields in the imaged slice. Independent temperature dependency experiments over the 13-38 °C range confirmed the greater stability of shorter vs longer T1|T2 tubes. Excellent long-term (12-month) reproducibility of measured T1|T2 was demonstrated across both field strengths (all coefficients of variation < 1.38%). CONCLUSION: The T2 mapping phantom demonstrates excellent structural integrity, B0 and B1 uniformity, and reproducibility of its internal tube T1|T2 out to 1 year. This device may now be mass-produced to support the quality assurance of T2 mapping in CMR

Challenging Occam’s razor: An unusual combination of sarcoidosis and amyloidosis. The value of CMR in infiltrative cardiomyopathies

We describe the case of a 66-year old woman with the extremely rare combination of sarcoidosis-amyloidosis (light-chain) and the important role of cardiovascular magnetic resonance imaging to differentiate between these two infiltrative diseases. Myocardial characterization with T1 mapping can improve disease detection especially in overlap cases and possibly obviate the need for cardiac biopsy