title: Volumetric magnetic resonance imaging of dorsal root ganglia for the objective quantitative assessment of neuron death after peripheral nerve injury.
abstract: Prevention of neuron death after peripheral nerve injury is vital to regaining adequate cutaneous innervation density and quality of sensation, and while experimentally proven neuroprotective therapies exist, there lacks suitable clinical outcome measures for translational research. Axotomized dorsal root ganglia (DRG) histologically exhibit volume reduction in proportion to the amount of neuronal death within them. Hence, this study evaluated the validity of using magnetic resonance imaging (MRI) to quantify DRG volume as a proxy measure of cell death. A high-resolution 3D MRI sequence was developed for volumetric quantification of the L4 DRG in the rat sciatic nerve model. An unoperated "control" group (n=4), and a "nerve transection" group (n=6), 4 weeks after axotomy, were scanned. Accuracy and validity of the technique were evaluated by comparison with morphological quantification of DRG volume and stereological counts of surviving neurons (optical fractionator). The technique was precise (coefficient of variation=4.3%), highly repeatable (9% variability), and sensitive (mean 15.0% volume reduction in axotomized ganglia detected with statistical significance: p<0.01). MRI showed strong and highly significant correlation with morphological measures of DRG volume loss (r=0.90, p<0.001), which in turn correlated well with neuron loss (r=0.75, p<0.05). MRI similarly exhibited direct correlation with neuron loss (r=0.67, p<0.05) with consistent agreement. MRI volumetric quantification of DRG is therefore a valid in vivo measure of neuron loss. As a non-invasive, objective measure of neuronal death after nerve trauma this technique has potential as a diagnostic modality and a quantitative tool for clinical studies of neuroprotective agents.
authors.affiliation: Blond McIndoe Research Laboratories, University of Manchester, 3.102 Stopford Building, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Christian A
authors.initials: CA
authors.lastname: West
authors.forename: Karen A
authors.initials: KA
authors.lastname: Davies
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hart
authors.forename: Mikael
authors.initials: M
authors.lastname: Wiberg
authors.forename: Steve R
authors.initials: SR
authors.lastname: Williams
authors.forename: Giorgio
authors.initials: G
authors.lastname: Terenghi
mesh_terms: D000818:Animals; D019771:Axotomy; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000473:pathology* / Q000503:physiopathology; D008159:Lumbar Vertebrae; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D009475:Neurons, Afferent / Q000473:pathology*; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000473:pathology* / Q000503:physiopathology; D011237:Predictive Value of Tests; D051381:Rats; D017207:Rats, Sprague-Dawley