Development of a Multi-Modality Imaging Approach to Evaluate Lupus Nephritis

Amit Saxena ¹, David Karp ², Brad Rovin ³, Mikael Boesen ⁴, Olga Kubassova ⁵, Claire Dykas ⁶, Anthony Yeo ⁷ and Peter Lipsky⁸, ¹New York University School of Medicine, New York, NY, ²UTSouthwestern Medical Center, Dallas, TX, ³The Ohio State University Medical Center, Columbus, OH, ⁴Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark, ⁵Image Analysis Group, London, United Kingdom, ⁶AmpelBioSolutions, Charlottesville, VA, ⁷RILITE Research Institute, Charlottesville, VA, ⁸AMPEL BioSolutions, LLC, Charlottesville, VA

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: Imaging, lupus nephritis and magnetic resonance imaging (MRI), Systemic lupus erythematosus (SLE)

Session Information

Date: Monday, November 11, 2019

Title: 4M120: SLE – Clinical IV: Lupus Nephritis (1914–1919)

Session Type: ACR Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: Lupus nephritis (LN) remains a significant cause of morbidity and mortality in subjects with Systemic Lupus Erythematosus (SLE). The gold standard for evaluation of LN remains the kidney biopsy, whereas renal function is usually evaluated by eGFR and urinary protein:creatinine ratio. More effective and sensitive methodology is needed to assess LN and also the response to treatment. Functional imaging of the kidney using quantitative techniques has great potential, as it can assess kidney function and pathologic changes non-invasively by evaluating perfusion, oxygenation, cellular density and fibrosis. The objective of this study was to develop a multi-modality imaging approach for the evaluation of the spectrum of pathologic changes in LN.

Methods: In this multi-center study (NCT03180021), subjects who were having a standard of care renal biopsy for LN were asked to participate in the imaging evaluation. Local Institutional Review Board approval was obtained, and subjects signed an Informed Consent Form. Dynamic contrast enhanced MRI (DCE-MRI) was employed to detect changes in vascularization and perfusion, Diffusion Weighted Imaging (DWI) to assess interstitial diffusion, T2*Map/BOLD to evaluate tissue oxygenation and T1rho to evaluate fibrosis (Figure 1). Regions of interest were identified in the imaged kidneys and imaging parameters were correlated with measures of renal function, including eGFR and urinary protein: creatinine ratio. In DCE-MRI, we specifically focused on mean Maximum Enhancement (ME), mean Time to Peak Enhancement (TTP) and mean Time of Washout (Twashout) as indicators of renal perfusion.

Results: Nine subjects have been evaluated to date and their imaging data assessed for quality. Evaluation of mean data from DCE-MRI has shown a significant correlation between renal perfusion and renal function. For example, the 24 hour protein concentration negatively correlated with ME (r_s=-0.81, p=0.015), TTP (r_s=-0.83, p=0.01) and Twashout (r_s=-0.81.p=0.01, Spearman rank correlation). In addition, the protein:creatinine ratio also negatively correlated with ME (r_s=-0.79, p=0.02), TTP (r_s=-0.74, p=0.04) and Twashout (r_s=-0.79, p=0.02, Spearman rank correlation).

Conclusion: These initial results have established the feasibility of multi-modality imaging as a tool to evaluate LN in a multi-center study. Moreover, changes in perfusion detected by DCE-MRI significantly correlate with proteinuria and urinary protein:creatinine ratio. These results suggest that multiparameter imaging may contribute useful data in the evaluation of subjects with LN.

Figure 1: Multi-modality imaging from a representative LN patient. Left: Map of the initial rate of enhancement -DYNAMIKA™- from DCE-MRI showing the degree of perfusion – the white-yellow colors correspond to increased and the redder colors decreased perfusion- in which decreased perfusion can be seen in the anterior pole of the right kidney ; Left center: DWI sequence that shows diffusion; Right center: T1rho illustrating fibrosis; and Right:T2*Map/BOLD to investigate tissue oxygenation within the renal medullary tissue.

Disclosure: A. Saxena, AstraZeneca, 5, Bristol Myers Squibb, 5, Bristol-Myers Squibb, 5, GlaxoSmithKline, 5, GSK, 5; D. Karp, None; B. Rovin, Genentech, Inc., 9, Admirx, 5, Alexion, 5, Aurinia, 5, Biogen, 5, Biomarin, 5, Bristol Myers Squibb, 5, Callidates, 5, ChemoCentryx, 2, 5, Chugai Pharmaceuticals, 5, EMD Serono, 2, 5, Genentech, 5, Janssen, 5, Lupus Foundation of America, 5, Mallinckrodt, 5, MedImmune, 5, Morphosys, 5, Novartis, 5, Omeros, 3, Pfizer, 5, Ra Pharmaceuticals, 5, Retrophin, 2, 5, Rigel, 2, 5, Takeda, 5, AstraZeneca, 2, Hoffman-La Roche, 2, Human Genome Sciences Inc., a GSK Company, 2, NIH/NIDDK, 2, RILITE Foundation, 2; M. Boesen, Image Analysis Group, OAK Foundation, EUROSTAR, 2, AbbVie, AstraZeneca, Carestream, Celgene Corporation, Eli Lilly, Esaote, Pfizer, Roche, Siemens, UCB – consultant, 5, Image Analysis Group, 9; O. Kubassova, Image Analysis Group, 1, 3, 4; C. Dykas, None; A. Yeo, Horizon Pharma, 3; P. Lipsky, Horizon, 5, Janssen Research & Development, LLC, 2.

To cite this abstract in AMA style:

Saxena A, Karp D, Rovin B, Boesen M, Kubassova O, Dykas C, Yeo A, Lipsky P. Development of a Multi-Modality Imaging Approach to Evaluate Lupus Nephritis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/development-of-a-multi-modality-imaging-approach-to-evaluate-lupus-nephritis/. Accessed .

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