Sensory neuron death after upper limb nerve injury and protective effect of repair: clinical evaluation using volumetric magnetic resonance imaging of dorsal root Ganglia.

BACKGROUND: Extensive death of sensory neurons after nerve trauma depletes the number of regenerating neurons, contributing to inadequate cutaneous innervation density and poor sensory recovery. Experimentally proven neuroprotective neoadjuvant drugs require noninvasive in vivo measures of neuron death to permit clinical trials. In animal models of nerve transection, magnetic resonance imaging (MRI) proved a valid tool for quantifying sensory neuron loss within dorsal root ganglia (DRG) by measuring consequent proportional shrinkage of respective ganglia. OBJECTIVE: This system is investigated for clinical application after upper limb nerve injury and microsurgical nerve repair. METHODS: A 3-T clinical magnet was used to image and measure volume (Cavalieri principle) of C7-T1 DRG in uninjured volunteers (controls, n = 14), hand amputees (unrepaired nerve injury, n = 5), and early nerve repair patients (median and ulnar nerves transected, microsurgical nerve repair within 24 hours, n = 4). RESULTS: MRI was well tolerated. Volumetric analysis was feasible in 74% of patients. A mean 14% volume reduction was found in amputees' C7 and C8 DRG (P < .001 vs controls). Volume loss was lower in median and ulnar nerve repair patients (mean 3% volume loss, P < .01 vs amputees), and varied among patients. T1 DRG volume remained unaffected. CONCLUSION: MRI provides noninvasive in vivo assessment of DRG volume as a proxy clinical measure of sensory neuron death. The significant decrease found after unrepaired nerve injury provides indirect clinical evidence of axotomy-induced neuronal death. This loss was less after nerve repair, indicating a neuroprotective benefit of early repair. Volumetric MRI has potential diagnostic applications and is a quantitative tool for clinical trials of neuroprotective therapies.

Sensory neurons of the human brachial plexus: a quantitative study employing optical fractionation and in vivo volumetric magnetic resonance imaging.

BACKGROUND: Extensive neuron death following peripheral nerve trauma is implicated in poor sensory recovery. Translational research for experimentally proven neuroprotective drugs requires knowledge of the numbers and distribution of sensory neurons in the human upper limb and a novel noninvasive clinical measure of neuron loss. OBJECTIVE: To compare optical fractionation and volumetric magnetic resonance imaging (MRI) of dorsal root ganglia (DRG) in histological quantification and objective clinical assessment of human brachial plexus sensory neurons. METHODS: Bilateral C5-T1 DRG were harvested from 5 human cadavers for stereological volume measurement and sensory neuron counts (optical fractionator). MRI scans were obtained from 14 healthy volunteers for volumetric analysis of C5-T1 DRG. RESULTS: The brachial plexus is innervated by 425,409 (standard deviation 15,596) sensory neurons with a significant difference in neuron counts and DRG volume between segmental levels (P < .001), with C7 ganglion containing the most. DRG volume correlated with neuron counts (r = 0.75, P < .001). Vertebral artery pulsation hindered C5 and 6 imaging, yet high-resolution MRI of C7, C8, and T1 DRG permitted unbiased volume measurement. In accord with histological analysis, MRI confirmed a significant difference between C7, C8, and T1 DRG volume (P < .001), interindividual variability (CV = 15.3%), and sex differences (P = .04). Slight right-left sided disparity in neuron counts (2.5%, P = .04) was possibly related to hand dominance, but no significant volume disparity existed. CONCLUSION: Neuron counts for the human brachial plexus are presented. These correlate with histological DRG volumes and concur with volumetric MRI results in human volunteers. Volumetric MRI of C7-T1 DRG is a legitimate noninvasive proxy measure of sensory neurons for clinical study.