Ultra-high field MRI for evaluation of rectal cancer stroma ex vivo : correlation with histopathology

Purpose or Objective: Current clinical MRI techniques in rectal cancer are unable to differentiate Stage T1 from T2 (invasion of muscularis propria) tumours, and the differentiation of tumour from desmoplastic reaction or fibrous tissue remains a challenge1. Diffusion tensor imaging (DTI) MRI has potential to assess collagen structure and organisation (anisotropy). To our knowledge, there have been no MRI studies assessing DTI MRI for rectal cancer ex vivo. The purpose of this study was to examine DTI MRI derived biomarkers of rectal cancer stromal heterogeneity at high field strength ex vivo

Shortening NMR diffusion experimental times

NMR diffusion measurements have become the method of choice for measuring diffusing due to their wide applicability, speed of measurement, enormous range of accessible diffusion coefficients (from gas ~10-6 m2s-1 to large polymers ~10-15 m2s-1), and the ability to measure diffusion over a specified timescale, Δ, which greatly adds to the power of NMR diffusion measurements as it allows the ability to probe porous media [1,2]. The weakness of NMR diffusion measurements lies in their inherent insensitivity. Consequently, many experiments are in theory possible but in practice would simply consume too much spectrometer time and therefore become impractical. Even in cases where the total measurement time is not a limitation, making the measurement faster expands the horizons of diffusion measurements to study reaction kinetics [3,4], as well as simply increasing throughput

Magnetic resonance imaging detects placental hypoxia and acidosis in mouse models of perturbed pregnancies

Endothelial dysfunction as a result of dysregulation of anti-angiogenic molecules secreted by the placenta leads to the maternal hypertensive response characteristic of the pregnancy complication of preeclampsia. Structural abnormalities in the placenta have been proposed to result in altered placental perfusion, placental oxidative stress, cellular damage and inflammation and the release of anti-angiogenic compounds into the maternal circulation. The exact link between these factors is unclear. Here we show, using Magnetic Resonance Imaging as a tool to examine placental changes in mouse models of perturbed pregnancies, that T2 contrast between distinct regions of the placenta is abolished at complete loss of blood flow. Alterations in T2 (spin-spin or transverse) relaxation times are explained as a consequence of hypoxia and acidosis within the tissue. Similar changes are observed in perturbed pregnancies, indicating that acidosis as well as hypoxia may be a feature of pregnancy complications such as preeclampsia and may play a prominent role in the signalling pathways that lead to the increased secretion of anti-angiogenic compounds

MRI detection of hepatic n-acetylcysteine uptake in mice

This proof-of-concept study looked at the feasibility of using a thiol–water proton exchange (i.e., CEST) MRI contrast to detect in vivo hepatic N-acetylcysteine (NAC) uptake. The feasibility of detecting NAC-induced glutathione (GSH) biosynthesis using CEST MRI was also investigated. The detectability of the GSH amide and NAC thiol CEST effect at B0 = 7 T was determined in phantom experiments and simulations. C57BL/6 mice were injected intravenously (IV) with 50 g L−1 NAC in PBS (pH 7) during MRI acquisition. The dynamic magnetisation transfer ratio (MTR) and partial Z-spectral data were generated from the acquisition of measurements of the upfield NAC thiol and downfield GSH amide CEST effects in the liver. The 1H-NMR spectroscopy on aqueous mouse liver extracts, post-NAC-injection, was performed to verify hepatic NAC uptake. The dynamic MTR and partial Z-spectral data revealed a significant attenuation of the mouse liver MR signal when a saturation pulse was applied at −2.7 ppm (i.e., NAC thiol proton resonance) after the IV injection of the NAC solution. The 1H-NMR data revealed the presence of hepatic NAC, which coincided strongly with the increased upfield MTR in the dynamic CEST data, providing strong evidence that hepatic NAC uptake was detected. However, this MTR enhancement was attributed to a combination of NAC thiol CEST and some other upfield MT-generating mechanism(s) to be identified in future studies. The detection of hepatic GSH via its amide CEST MRI contrast was inconclusive based on the current results

Measuring signal amplitude : lizard brain atlas

There are many types of NMR experiment where it is necessary to extract the amplitude of a spectral peak relative to its amplitude from a previous iteration of the sequence. Pulsed Gradient Spin Echo (PGSE) and Pulsed Gradient Stimulated Echo (PGSTE) diffusion measurements fall into this category since the attenuation of the peak gives us the diffusion coefficient. Similarly, T1 and T2 measurements rely on the measurement of relative spectral peak heights. Typically, peak intensity is measured by either integrating under the absorption Lorentzian peak or taking its amplitude. In a recent and ongoing project using simulated noisy spectra, these methods were compared with each other and with a method that involves fitting a Lorentzian curve directly to the spectrum or a decaying complex exponential to the FID using Levenberg-Marquardt non-linear least squares fitting. The results indicate that the best method of extracting signal intensity is to use a matched filter and then to measure the amplitude of the peak of interest. The second part of the presentation will focus on the recent publication of a 3D MRI-based atlas of a lizard brain using data from a long running project with Daniel Hoops from ANU (at the time of the project) and now at McGill University and initiated through the National Imaging Facility (NIF) [1-3]. The 3D-MRI model of a tawny dragon brain is available for viewing online and can be downloaded from the Wiley Biolucida Server at wiley.biolucida.net

Applying X-ray micro-tomography to learning and memory

Metabolic processes and neural pathways such as those for glucose metabolism and olfaction in insects are similar to, and in some cases identical to, those found in vertebrates. In particular, the peripheral architecture of the insect and mammalian olfactory system is surprisingly similar. Thus one insect, the western honeybee (Apis mellifera), has become a model organism for the investigation of olfactory signal processing in the brain. A. Mellifera has superior abilities to identify, classify, learn and remember odoriferous environmental chemicals. The use of x-ray MicroCT imaging for the non-invasive study of insects (termed diagnostic radioentomology 'DR') is increasing. This experiment was conducted as a 'proof of principle' study to identify whether DR scanning live insects (honeybees) can be used to non-invasively examine learning and memory with respect to brain architecture and function. A bench-top MicroCT scanner was used to scan live bees. To enhance tissue differentiation, radiographic contrast was injected directly into the haemolymph. Brain volume was measured using BeeView software. Gross brain architecture was visualised in 2D and 3D projections. Scanning of live bees enabled minimally-invasive imaging of physiological processes for the first time such as passage of contrast from gut to haemolymph as well as preliminary brain perfusion studies. In particular, the learning and memory neuropils in the antennal lobes were assessed by measuring changes in antennal lobe volumes. Future experiments will correlate neuropil volume changes with classic PER learning and memory studies. One advantage of using an insect model is that multiple experiments can be conducted without the need for lengthy ethics approvals that apply to vertebrate experiments. The advantage of using live insects is that longitudinal studies can be performed on individuals therefore reducing, to a great extent, the inherent inter-cohort errors which occur. Once proof of principles is established in the insect model, experiments such as these can easily be extended to vertebrates

NMR imaging and diffusion

Magnetic resonance in the guise of conventional imaging (MRI, also known as k-space imaging) and diffusion imaging (q-space imaging) and combined k- and q-space imaging provides a powerful means of probing porous media and the dynamic processes occurring within such media. This article provides an overview of the imaging process and the accessible length scales of these techniques for probing porous media as well as the type of information that can be obtained. Image reconstruction as well as sources of artefacts are also covered in detail. Some applications of these techniques are also reviewed. Particular problems related to measurements in nanoporous systems are highlighted

Efficient and precise calculation of b-matrix elements in diffusion-weighted imaging pulse sequences

Precise NMR diffusion measurements require detailed knowledge of the cumulative dephasing effect caused by the numerous gradient pulses present in most NMR pulse sequences. This effect, which ultimately manifests itself as the diffusion-related NMR signal attenuation, is usually described by the b-value or the b-matrix in the case of multidirectional diffusion weighting, the latter being common in diffusion-weighted NMR imaging. Neglecting some of the gradient pulses introduces an error in the calculated diffusion coefficient reaching in some cases 100% of the expected value. Therefore, ensuring the b-matrix calculation includes all the known gradient pulses leads to significant error reduction. Calculation of the b-matrix for simple gradient waveforms is rather straightforward, yet it grows cumbersome when complexly shaped and/or numerous gradient pulses are introduced. Making three broad assumptions about the gradient pulse arrangement in a sequence results in an efficient framework for calculation of b-matrices as well providing some insight into optimal gradient pulse placement. The framework allows accounting for the diffusion-sensitising effect of complexly shaped gradient waveforms with modest computational time and power. This is achieved by using the b-matrix elements of the simple unmodified pulse sequence and minimising the integration of the complexly shaped gradient waveform in the modified sequence. Such re-evaluation of the b-matrix elements retains all the analytical relevance of the straightforward approach, yet at least halves the amount of symbolic integration required. The application of the framework is demonstrated with the evaluation of the expression describing the diffusion-sensitizing effect, caused by different bipolar gradient pulse modules

Low-bandwidth space/frequency component separation for quantitative imaging

Quantitative MRI is often used to analyse multicomponent systems. The analysis requires the contributions from different species to be isolated. Species with distinct chemical shifts can be separated by using a low acquisition bandwidth, which is easy to achieve in common quantitative imaging protocols. The bandwidth reduction leads to separation of NMR contributions from different species in the image space. This new method was implemented and tested on two multicomponent systems containing several spectrally and spatially unresolved components with both distinctly different and similar diffusion coefficients and relaxation times. Separation was achieved with routine MRI diffusion and relaxation measurement pulse sequences in a microimaging environment for water/polyethylene glycol solution and for chloroform/TMS/polyethylene glycol solution. Conventional monoexponential fitting was used to determine diffusion coefficients and relaxation times from the spectrally separated data, whereas biexponential or triexponential fitting was required in the unseparated reference experiments. In the two-component sample, the variation in the determined fast diffusing components was on the same order of magnitude for all experiments, while the variation in the slow diffusing polyethylene glycol was larger when no separation was present. The separation technique provided lower variability for all the determined diffusion coefficients and relaxation times in the three-component sample. The low-bandwidth separation method can provide separation of multicomponent systems based on the chemical shift difference between the species. The accuracy of the technique is comparable with the commonly used methods for bicomponent system analysis and surpasses those when there are more than two components in the sample

Is it time to forgo the use of the terms "spin-lattice" and "spin-spin" relaxation in NMR and MRI?

Spin relaxation is one of the most fundamental concepts in magnetic resonance and is one of the key NMR “observables” providing critical motional information in chemical systems and, by extension, diagnostic information in clinical imaging. Yet, it can be difficult to find accurate conceptual descriptions of the two relaxation processeslongitudinal and transversein the NMR or MRI literature that explain why these processes are also referred to as “spin−lattice” and “spin−spin” relaxation, respectively. Often, the explanations provided in terms of energy levels, energy exchange, and the loss of phase coherence are inaccurate oversimplifications of quantum mechanical concepts and are thus incomplete and, at times, even contradictory. In fact, various texts still follow the terminology proposed >7 decades ago largely based on the theory of NMR in solids, even though it is clearly inadequate in the case of solution-state NMR. Here, we present the fundamental and quantum mechanical explanations of both relaxation processes in simple terms while clarifying and discussing the potential origins of some common confusions, nuances in the terminology, and seemingly contradictory definitions and explanations in the literature. Considering the issues with the old and inaccurate terminology, the consistent use of an alternate and more generally applicable terminology is proposed