Search

The VERDICT framework for modelling diffusion MRI data aims to relate parameters from a biophysical model to histological features used for tumour grading in prostate cancer. Validation of the VERDICT model is necessary for clinical use. This study compared VERDICT parameters obtained ex vivo with histology in five specimens from radical prostatectomy. A patient-specific 3D-printed mould was used to investigate the effects of fixation on VERDICT parameters and to aid registration to histology. A rich diffusion data set was acquired in each ex vivo prostate before and after fixation. At both time points, data were best described by a two-compartment model: the model assumes that an anisotropic tensor compartment represents the extracellular space and a restricted sphere compartment models the intracellular space. The effect of fixation on model parameters associated with tissue microstructure was small. The patient-specific mould minimized tissue deformations and co-localized slices, so that rigid registration of MRI to histology images allowed region-based comparison with histology. The VERDICT estimate of the intracellular volume fraction corresponded to histological indicators of cellular fraction, including high values in tumour regions. The average sphere radius from VERDICT, representing the average cell size, was relatively uniform across samples. The primary diffusion direction from the extracellular compartment of the VERDICT model aligned with collagen fibre patterns in the stroma obtained by structure tensor analysis. This confirmed the biophysical relationship between ex vivo VERDICT parameters and tissue microstructure from histology.

The permeability of cell membranes varies significantly across both healthy and diseased tissue, and changes in cell membrane permeability can occur during treatment response in tumours. Measurements of cell membrane permeability could therefore be useful for tumour detection and as biomarkers of treatment response in the clinic. As the diffusion of water across the cell membrane is directly dependent on cell membrane permeability, we have investigated the ability of diffusion-diffusion exchange spectroscopy to quantify the diffusion exchange of water in a suspension of yeast, as a first step towards its application in tumours.

The glymphatics system describes a CSF-mediated clearance pathway for the removal of potentially harmful molecules, such as amyloid beta, from the brain. As such, its components may represent new therapeutic targets to alleviate aberrant protein accumulation that defines the most prevalent neurodegenerative conditions. Currently, however, the absence of any non-invasive measurement technique prohibits detailed understanding of glymphatic function in the human brain and in turn, it’s role in pathology. Here, we present the first non-invasive technique for the assessment of glymphatic inflow by using an ultra-long echo time, low b-value, multi-direction diffusion weighted MRI sequence to assess perivascular fluid movement (which represents a critical component of the glymphatic pathway) in the rat brain. This novel, quantitative and non-invasive approach may represent a valuable biomarker of CSF-mediated brain clearance, working towards the clinical need for reliable and early diagnostic indicators of neurodegenerative conditions such as Alzheimer’s disease., eLife digest Our brain is bathed in cerebrospinal fluid, a clear liquid that ‘cushions’ the fragile organ. This liquid travels into the brain along special channels – the perivascular space – that surround certain blood vessels. As the fluid washes in and out of the brain, it takes with it potentially harmful molecules, such as the aggregates that build up to cause Alzheimer’s disease. If this brain-cleaning system becomes faulty, it could lead to neurodegenerative diseases. However, it is extremely difficult to measure the activity of this intricate and delicate system, and most studies so far have had to use invasive techniques that usually require brain surgery. Now, Harrison et al. adapt a technique, called diffusion tensor magnetic resonance imaging (MRI), to visualise how the cerebrospinal fluid moves in the perivascular space in healthy rats. The non-invasive MRI method captures how the cerebrospinal fluid is driven into the brain when the blood vessels nearby expand and contract; as the vessels pulsate with each heartbeat, there is a 300% increase in the movement of the fluid in the perivascular space. This approach could be applied to understand exactly how neurodegenerative diseases emerge when the cerebrospinal fluid stops to properly clean the brain. Ultimately, the method could be used to detect when the cleansing system starts to fail in people, which could help to treat patients before their brains accumulate too many harmful substances.

The diffusion signal in breast tissue has primarily been modelled using apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM) and diffusion tensor (DT) models, which may be too simplistic to describe the underlying tissue microstructure. Formalin-fixed breast cancer samples were scanned using a wide range of gradient strengths, durations, separations and orientations. A variety of one- and two-compartment models were tested to determine which best described the data. Models with restricted diffusion components and anisotropy were selected in most cancerous regions and there were no regions in which conventional ADC or DT models were selected. Maps of ADC generally related to cellularity on histology, but maps of parameters from more complex models suggest that both overall cell volume fraction and individual cell size can contribute to the diffusion signal, affecting the specificity of ADC to the tissue microstructure. The areas of coherence in diffusion anisotropy images were small, approximately 1 mm, but the orientation corresponded to stromal orientation patterns on histology.

The estimation of axon radius provides insights into brain function [1] and could provide progression and classification biomarkers for a number of white matter diseases [2-4]. A recent in silico study [5] has shown that optimised gradient waveforms (GEN) and oscillating gradient waveform spin echo (OGSE) have increased sensitivity to small axon radius compared to pulsed gradient spin echo (PGSE) diffusion MR sequences. In a follow-up study [6], experiments with glass capillaries show the practical feasibility of GEN sequences and verify improved pore-size estimates. Here, we compare PGSE with sine, sine with arbitrary phase, and square wave OGSE (SNOGSE, SPOGSE, SWOGSE, respectively) for axon radius mapping in the corpus callosum of a rat, ex-vivo. Our results suggest improvements in pore size estimates from OGSE over PGSE, with greatest improvement from SWOGSE, supporting theoretical results from [5] and other studies [7-9].