Abstract
ObjectiveQuantitative magnetic resonance imaging was used to determine partition coefficients and characteristic time constants for diffusion of MRI contrast agents in disc tissue.Materials and methodsTwenty-two excised equine intervertebral discs were exposed to a range of contrast agents: six to manganese chloride, eight to Magnevist (gadopentetate dimeglumine) and eight to Gadovist (gadobutrol), and uptake into the disc was quantified in T1-weighted images.ResultsDiffusion for all contrast agents was approximately 25% faster in the nucleus than in the outer annulus; disc-average time constants ranged from (2.28 ± 0.23) × 104 s for Gadovist (uncharged, molecular mass 605 g/mol) to (5.07 ± 0.75) × 104 s for the manganese cation (charge + 2). Disc-average partition coefficients ranged from 0.77 ± 0.04 for the anion in Magnevist (charge − 2, molecular mass 548 g/mol) to 5.14 ± 0.43 for the manganese cation.ConclusionThe MRI technique provides high-quality quantitative data which correspond well to theoretical predictions, allowing values for partition coefficient and time constant to be readily determined. These measurements provide information to underpin similar studies in vivo and may be used as a model for the transport of nutrients and pharmaceutical agents in the disc.
Highlights
Seventy percent of the world’s population suffers from low back pain [1] and it imposes a costly burden in terms of health care and loss of productivity at work [2]
A quantity of 0.15 M NaCl, pH 7.4, fills the space immediately around the disc to maintain hydration and provides a transport pathway; the two compartments on either side of the membranes are filled with 0.15 M NaCl containing 10% w/v polyethylene glycol (PEG), molecular mass 20,000 g/mol. (Preliminary experiments established that this concentration of PEG maintained the initial hydration over several hours.) The disc was allowed to equilibrate in the chamber for at least 1 h before the start of the imaging experiment; after some initial images the NaCl/PEG medium was exchanged for a similar medium to which an MRI contrast agent had been added
The experimental data for each region of each sample were fitted to an exponential of the form given by Eq 3 except in a few cases, where the time constant τ was very long, so that the exponential part of the time course was not established before the end of the measurement period—in those cases the data were fitted to Eq 2. (In a very small number of cases—two from 286—no convincing curve fit was possible.) Each curve fit gave values for the amplitude B and the time constant τ
Summary
Seventy percent of the world’s population suffers from low back pain [1] and it imposes a costly burden in terms of health care and loss of productivity at work [2]. By the age of 49, 97% of lumbar intervertebral discs show some degeneration [4]. There is difficulty in distinguishing between natural ageing and pathological disorders of the intervertebral disc [2], many authors (e.g., [1]) have expressed the hope of slowing the process of degeneration, or even reversing it, to benefit patients. Cells at the centre of the disc can be as far as 8 mm from the nearest blood vessel [5] and are reliant for their nutrition on transport of solutes through the extracellular matrix [6, 7]. The mechanisms and factors determining the rate of transport are still not well understood [10, 11], in part due to technical difficulties in investigating solute transport in the disc in vivo
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