Noninvasive Detection of Radiation-Induced Optic Neuropathy by Manganese-Enhanced MRI

Abstract

Available imaging techniques have a limited ability to detect radiation-induced injury of the normal brain. In particular, there is no noninvasive method available for detection of structural or functional neuronal damage induced by radiation. This study was designed to determine whether MRI enhanced using the neuronal track tracer MnCl(2) can detect radiation-induced optic neuropathy. A single dose of radiation (35 Gy) was delivered to produce optic neuropathy in Fischer 344 rats by using a stereotactic method with a 6-mm dorsoventral secondary collimator. At 6 months after irradiation, MRI was performed in 1-mm sections using a 7-T magnetic field with the neuronal tracer MnCl(2) injected into the vitreous of the eye 24 h prior to imaging. The rats were then killed humanely for a histological study with hematoxylin and eosin, glial fibrillary acidic protein (Gfap) for the detection of astrocytic activity, Luxol Fast Blue/Periodic Acid Schiff (LFB/PAS) for the detection of myelinization status, and Bielschowski silver stain for axon status. In nonirradiated control animals, T1-weighted MRI with manganese vitreous injection revealed an optic nerve track that was brightly enhanced from the orbit to the optic chiasm. In the irradiated animals, there was clear evidence of the damage at the optic chiasm and optic nerves, with loss of axon and demyelinization within the site of irradiation upon histological examination. T1-weighted MRI with manganese vitreous injection showed an enhancing optic nerve posterior to the orbit. However, this enhancement disappeared at the site of irradiation. The area of loss of manganese contrast on the MRI scan correlated well with the area of histological abnormality showing axonal degeneration and demyelinization. Radiation-induced optic neuropathy was thus detected noninvasively by MRI with the antegrade neuronal tracer manganese, which exhibited negative contrast enhancement by causing loss of signal. This study represents the first demonstration of MR imaging of radiation-induced neuronal damage and could provide a means to explore the biological and functional integrity of neuronal pathways.

Manganese‐enhanced magnetic resonance imaging (MEMRI): methodological and practical considerations

“…The use of MRI to measure the transport of Mn 2þ down the optic nerve has been shown to be a sensitive indicator of damage to the nerve due to radiation. 11 This is a clear indication that MEMRI tract-tracing will be useful to study damage and repair of neural connections.…”

“…1,3,4 The second use of MEMRI is to trace specific neuronal connections in the brain. MEMRI has been shown to enable imaging anterograde connections in the olfactory, 7,8 visual, [9][10][11] and somatosensory pathways 12 of the rat and mouse brain after direct injection of MnCl 2 into a specific brain region. The song centers of the bird 13 and neural connections in the monkey 14 have also been mapped with MEMRI neuronal tracing techniques.…”

MR Imaging of Papilledema and Visual Pathways: Effects of Increased Intracranial Pressure and Pathophysiologic Mechanisms

“…52 While not applicable to human studies, manganese-enhanced MR imaging may give additional insight into ON function by using the property of manganese uptake by active neurons to image neural activity. [53][54][55][56][57] Visualization of the fiber tracts from the retina to the visual cortex is also being investigated with DTI. 58,59 DTI can map optic radiations within the brain with a great deal of accuracy compared with postmortem dissections.…”

Prognostic MRI biomarkers of treatment efficacy for retinopathy

“…Other studies have investigated intravitreally administered Mn 2þ to highlight the optic nerve and examine its transport (13,(71)(72)(73)(74). This is a promising approach which can provide unique information.…”