Bioxydyn has delivered multiple studies for pharmaceutical companies using quantitative imaging of inflammation in a wide range of diseases, including functional imaging of joints in rheumatoid arthritis and osteoarthritis and renal imaging in nephritis.
We use dynamic contrast-enhanced MRI (DCE-MRI) to quantify changes in perfusion and endothelial integrity in the presence of inflammation and during treatment. Bioxydyn has defined many of the standard approaches to the technique’s implementation in clinical trials.
DCE-MRI involves the use of standard clinical intravenously-administered gadolinium-based contrast agents. The uptake and washout of the agent is interpreted using physiological modelling methods to provide imaging biomarkers of microvascular function and inflammation.
Bioxydyn uses the Ktrans quantitative biomarker, which can be readily compared between centres. Its relationship to the intensity of inflammation is based on sound and widely accepted science, is extremely sensitive to drug effects, and only requires small patient numbers. The images show change in Ktrans in the joints of the hands and wrist in an individual with rheumatoid arthritis during therapeutic intervention.
Bioxydyn is also experienced in using MRI biomarkers of inflammation and fibrosis in kidney disease. Examples include measurements of perfusion derived from arterial spin labelling (ASL), relaxation time measurements (T1, T2, T2*), volume measurements, diffusion MRI (ADC, FA). We are also experts in methods to measure hypoxic status (BOLD, oxygen-enhanced MRI) and pH (CEST).
The image shows maps of T2* in the kidneys of an individual with lupus nephritis. From Skeoch et al 2017.
Genovese MC, Berkowitz M, Conaghan PG, Peterfy C, Davy K, Fisheleva E, Gupta A, Inman D, Janiczek R, Layton M, Mitchell N, Patel J, Roberts A, Saurigny D, Smith JE, Williamson R, Tak PP, MRI of the joint and evaluation of the granulocyte-macrophage colony-stimulating factor-CCL17 axis in patients with rheumatoid arthritis receiving otilimab: a phase 2a randomised mechanistic study. Lancet Rheumatol. 2020 Nov;2(11):e666-e676.
Schett G, Bainbridge C, Berkowitz M, Davy K, Fernandes S, Griep E, Harrison S, Gupta A, Lloyd-Hughes J, Roberts A, Layton M, Nowak NA, Patel J, Rech J, Smith JE, Watts S, Tak PP, Anti-granulocyte-macrophage colony-stimulating factor antibody otilimab in patients with hand osteoarthritis: a phase 2a randomised trial. Lancet Rheumatol. 2020 Oct;2(10):e623-e632.
Alyami A, Hoad CL, Tench C, Bannur U, Clarke C, Latief K, Argyriou K, Lobo A, Lung P, Baldwin-Cleland R, Sahnan K, Hart A, Limdi JK, Mclaughlin J, Atkinson D, Parker GJM, O'Connor JPB, Little RA, Gowland PA, Moran GW, Quantitative Magnetic Resonance Imaging in Perianal Crohn's Disease at 1.5 and 3.0 T: A Feasibility Study. Diagnostics (Basel). 2021 Nov 17;11(11):.
MacKay JW, Nezhad FS, Rifai T, Kaggie JD, Naish JH, Roberts C, Graves MJ, Waterton JC, Janiczek RL, Roberts AR, McCaskie A, Gilbert FJ, Parker GJM, Dynamic contrast-enhanced MRI of synovitis in knee osteoarthritis: repeatability, discrimination and sensitivity to change in a prospective experimental study. Eur Radiol. 2021 Aug;31(8):5746-5758.
Mitsides N, Alsehli FMS, Mc Hough D, Shalamanova L, Wilkinson F, Alderdice J, Mitra R, Swiecicka A, Brenchley P, Parker GJM, Alexander MY, Mitra S, Salt and Water Retention Is Associated with Microinflammation and Endothelial Injury in Chronic Kidney Disease. Nephron. 2019;143(4):234-242.
Abid KA, Sobowale OA, Parkes LM, Naish J, Parker GJM, du Plessis D, Brough D, Barrington J, Allan SM, Hinz R, Parry-Jones AR, Assessing Inflammation in Acute Intracerebral Hemorrhage with PK11195 PET and Dynamic Contrast-Enhanced MRI. J Neuroimaging. 2018 Mar;28(2):158-161.
Skeoch S, Hubbard Cristinacce PL, Dobbs M, Naish J, Woodhouse N, Ho M, Waterton JC, Parker GJM, Bruce IN, Evaluation of non-contrast MRI biomarkers in lupus nephritis. Clin Exp Rheumatol. 2017 Nov-Dec;35(6):954-958.
Waterton JC, Ho M, Nordenmark LH, Jenkins M, DiCarlo J, Guillard G, Roberts C, Buonaccorsi G, Parker GJM, Bowes MA, Peterfy C, Kellner H, Taylor PC, Repeatability and response to therapy of dynamic contrast-enhanced magnetic resonance imaging biomarkers in rheumatoid arthritis in a large multicentre trial setting. Eur Radiol. 2017 Sep;27(9):3662-3668.
Tiddens HA, Stick SM, Wild JM, Ciet P, Parker GJ, Koch A, Vogel-Claussen J, Respiratory tract exacerbations revisited: ventilation, inflammation, perfusion, and structure (VIPS) monitoring to redefine treatment. Pediatr Pulmonol. 2015 Oct;50 Suppl 40:S57-65.
Williams TG, Holmes AP, Waterton JC, Maciewicz RA, Hutchinson CE, Moots RJ, Nash AF, Taylor CJ, Anatomically corresponded regional analysis of cartilage in asymptomatic and osteoarthritic knees by statistical shape modelling of the bone. IEEE Trans Med Imaging. 2010 Aug;29(8):1541-59.
Creamer P, Keen M, Zananiri F, Waterton JC, Maciewicz RA, Oliver C, Dieppe P, Watt I, Quantitative magnetic resonance imaging of the knee: a method of measuring response to intra-articular treatments. Ann Rheum Dis. 1997 Jun;56(6):378-81.
