Chromium(VI) as a novel MRI contrast agent for cerebral white matter: Preliminary results in mouse brain in vivo

Abstract

This work demonstrates that intraventricular microinjections of a low dose of potassium dichromate (0.4 L of 10 mM solution) yield a specific contrast enhancement of white matter (WM) tracts in T 1 -weighted 3D MRI of mouse brain in vivo. Pronounced and persistent signal increases (40 -100% at 24 hr after injection) were observed in the corpus callosum, anterior commissure, fornix, and stria medullaris, as well as in the mammillothalamic tract and fasciculus retroflexus. These results suggest that the extracellular diffusion of diamagnetic chromium(VI) (Cr(VI)) after injection is followed by a tissue-specific reduction to paramagnetic Cr(V) and ( In neuroanatomy, specific chemical reactions of lipids exposed to aqueous solutions of potassium dichromate (K 2 Cr 2 O 7 with chromium in redox state Cr(VI)) have been used for histological staining of myelin. For example, in a previous study based on Weigert-Smith-Dietrich procedures, myelin sheaths in white matter (WM) tracts in rat brain were identified by controlled chromation of lipids, which was accompanied by a simultaneous reduction of Cr(VI) (1). The present work attempts to exploit such principles for cerebral MRI of WM. The idea is based on the assumption that a reduction of diamagnetic Cr(VI) to paramagnetic Cr(V) and Cr(III) by lipid oxidation causes a shortening of the T 1 relaxation time of surrounding water and/or lipid protons.Using sodium dichromate to study the metabolism of chromium species in biochemical reactions occurring on the skin of living rats, Liu and coworkers (2) demonstrated the potential of Cr(VI) for in vivo EPR spectroscopy. Similarly, the formation of Cr(V) and Cr(III) was detected by MRI after injection of sodium dichromate in the kidney and liver of a mouse in vivo (3), and of potassium chromate in the lung of a rat postmortem (4). The purposes of this first Cr(VI)-enhanced MRI study of mouse brain in vivo were to 1) examine whether a direct injection of a small amount of Cr(VI) induces a contrast enhancement detectable by T 1 -weighted 3D MRI, 2) determine the structures highlighted in the intact living brain, and 3) discuss putative histochemical and physiological mechanisms and how they differ from other paramagnetic MRI contrast agents.

<i>In Vivo</i> Brain MR Imaging at Subnanoliter Resolution: Contrast and Histology

“…Distributed over the cerebrospinal and extracellular fluid of the entire central nervous system, the chelates induce a unique contrast in brain MR imaging. 19,[39][40][41][42][43] In GM, the resulting contrasts are in excellent agreement with histological stains of intracellular compounds. 19 For example, as shown in the cerebellum (Fig.…”

Classification and basic properties of contrast agents for magnetic resonance imaging

“…Cr(VI)-induced contrast leads to only a small nonspecific enhancement of gray matter structures, such as the hippocampus. Thus, this method reveals novel information that differs from that obtainable using Mn 2þ injection (73).…”

Increased anatomical detail by in vitro MR microscopy with a modified Golgi impregnation method

“…Based on the assumption that a reduction of diamagnetic hexavalent chromium to paramagnetic Cr(III) by lipid oxidation would cause a shortening of the T 1 and T 2 of surrounding water and/or lipid protons, potassium dichromate has been studied as an MRI contrast agent (5). As reported recently, the extracellular diffusion of K 2 (Cr 2 O 7 ) after intraventricular injection leads to a mild enhancement of white matter structures (6).…”

“…The specific oxidation of lipids exposed to aqueous solutions of potassium dichromate has been used for histologic staining of myelin (4). It has been suggested that a set of substances in the chromation, such as formaldehyde, sucrose, or hydrogen peroxide, reduces the hexavalent chromium (Cr(VI)) of the potassium dichromate to trivalent chromium (Cr(III)) (5–7). Based on the assumption that a reduction of diamagnetic hexavalent chromium to paramagnetic Cr(III) by lipid oxidation would cause a shortening of the T 1 and T 2 of surrounding water and/or lipid protons, potassium dichromate has been studied as an MRI contrast agent (5).…”