SuperResPath-Renal: Quantitative super-resolution technology for a fast, de-centralised clinical diagnosis of renal pathologies

Background Renal pathologies are the most common primary cause of nephrotic syndrome.

For diagnosis, a renal biopsy is examined at different levels, including high-resolution electron microscopy (EM) to detect glomerular ultrastructural changes imperceptible by histology.

EM is the most expensive single test in histopathology labs, limiting diagnosis of renal pathologies with long turnaround times (2-3 weeks).

NHS England spent around £1.45 billion on chronic kidney disease (2009-10), with an average 70% of renal biopsies needing EM studies for diagnosis, costing around £300 each.

Aims and Research question Our project aims to combine super-resolution microscopy with advanced data analysis to establish a de-centralised and rapid (2-5 days) platform for routine renal pathology assessment.

We intend to detect multiple glomerular podocyte markers in biopsy samples using high-precision dSTORM imaging for an improved renal histopathology diagnosis and patient outcome.

Methods Formalin-fixed paraffin-embedded tissue samples will be imaged using ONI s Nanoimager microscope, with cutting-edge super-resolution imaging technology.

Machine-learning algorithms will allow detection of features of interest to be imaged with dSTORM to visualise key fluorescently-labelled renal proteins. Multi-parametric cluster-based data analysis will provide a read-out for diseased tissues.

Timelines Phase I will validate and optimise the protocol to stain tissue samples for dSTORM imaging, phase II will integrate imaging and automated data analysis into a turn-key workflow, phase III will see the clinical application of ONI's super-resolution microscope into NHS histopathology labs. Our technology should be patient-ready in 3-years.

Anticipated impact and dissemination Our technology will allow a larger portion of renal biopsies to be examined, increasing diagnostic sensitivity and specificity, benefiting patients.

Replacing EM and reducing labour costs could save money to the NHS (>£10M across UK pathology units, 3-years post-project).

Adoption will be ensured through conference presentations, publications, demonstrations at NHS pathology units, and with public and patient involvement.