A Caltech Library Service

Longitudinal manganese-enhanced magnetic resonance imaging of neural projections and activity

Uselman, Taylor W. and Medina, Christopher S. and Gray, Harry B. and Jacobs, Russell E. and Bearer, Elaine L. (2022) Longitudinal manganese-enhanced magnetic resonance imaging of neural projections and activity. NMR in Biomedicine, 35 (6). Art. No. e4675. ISSN 0952-3480. doi:10.1002/nbm.4675.

Full text is not posted in this repository. Consult Related URLs below.

Use this Persistent URL to link to this item:


Manganese-enhanced magnetic resonance imaging (MEMRI) holds exceptional promise for preclinical studies of brain-wide physiology in awake-behaving animals. The objectives of this review are to update the current information regarding MEMRI and to inform new investigators as to its potential. Mn(II) is a powerful contrast agent for two main reasons: (1) high signal intensity at low doses; and (2) biological interactions, such as projection tracing and neural activity mapping via entry into electrically active neurons in the living brain. High-spin Mn(II) reduces the relaxation time of water protons: at Mn(II) concentrations typically encountered in MEMRI, robust hyperintensity is obtained without adverse effects. By selectively entering neurons through voltage-gated calcium channels, Mn(II) highlights active neurons. Safe doses may be repeated over weeks to allow for longitudinal imaging of brain-wide dynamics in the same individual across time. When delivered by stereotactic intracerebral injection, Mn(II) enters active neurons at the injection site and then travels inside axons for long distances, tracing neuronal projection anatomy. Rates of axonal transport within the brain were measured for the first time in “time-lapse” MEMRI. When delivered systemically, Mn(II) enters active neurons throughout the brain via voltage-sensitive calcium channels and clears slowly. Thus behavior can be monitored during Mn(II) uptake and hyperintense signals due to Mn(II) uptake captured retrospectively, allowing pairing of behavior with neural activity maps for the first time. Here we review critical information gained from MEMRI projection mapping about human neuropsychological disorders. We then discuss results from neural activity mapping from systemic Mn(II) imaged longitudinally that have illuminated development of the tonotopic map in the inferior colliculus as well as brain-wide responses to acute threat and how it evolves over time. MEMRI posed specific challenges for image data analysis that have recently been transcended. We predict a bright future for longitudinal MEMRI in pursuit of solutions to the brain-behavior mystery.

Item Type:Article
Related URLs:
URLURL TypeDescription
Uselman, Taylor W.0000-0002-3856-5248
Medina, Christopher S.0000-0002-2545-6536
Gray, Harry B.0000-0002-7937-7876
Jacobs, Russell E.0000-0002-1382-8486
Bearer, Elaine L.0000-0002-8390-8529
Additional Information:© 2022 John Wiley & Sons, Ltd. Issue Online: 19 May 2022; Version of Record online: 06 March 2022; Manuscript accepted: 07 December 2021; Manuscript revised: 19 October 2021; Manuscript received: 28 July 2021. Funding information: Arnold and Mabel Beckman Foundation; Beckman Institute, California Institute of Technology; Brain and Behavioral Health Institute, UNM; Harvey Family Endowment; Zilkha Neurogenetic Institute, Keck School of Medicine, USC; National Institutes of Health; National Institute on Aging; National Institute on Drug Abuse; National Institute of General Medical Sciences; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke Data Availability Statement: Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
Funding AgencyGrant Number
Arnold and Mabel Beckman FoundationUNSPECIFIED
Caltech Beckman InstituteUNSPECIFIED
Brain and Behavioral Health InstituteUNSPECIFIED
Harvey Family EndowmentUNSPECIFIED
Zilkha Neurogenetic InstituteUNSPECIFIED
Subject Keywords:brain-wide activity mapping; computational image analysis; longitudinal imaging; manganese; magnetic resonance imaging; rodent brain imaging; T₁-weighted imaging, tract-tracing
Issue or Number:6
Record Number:CaltechAUTHORS:20220307-188059000
Persistent URL:
Official Citation:Uselman, TW, Medina, CS, Gray, HB, Jacobs, RE, Bearer, EL. Longitudinal manganese-enhanced magnetic resonance imaging of neural projections and activity. NMR in Biomedicine. 2022; 35(6):e4675. doi:10.1002/nbm.4675
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:113761
Deposited By: George Porter
Deposited On:08 Mar 2022 23:23
Last Modified:07 Jun 2022 20:33

Repository Staff Only: item control page