Molecular Imaging Branch (MIB)

Goals

Established by the NIMH in 2000, the Molecular Imaging Branch (MIB) uses a variety of neuroimaging techniques to explore molecular and chemical mechanisms associated with neural function in health and disease. The overall goal of the Branch is to further elucidate pathophysiological mechanisms associated with neuropsychiatric disorders, with the expectation that such knowledge will ultimately decrease the burden of these illnesses by helping guide the development and evaluation of improved therapeutics for these disorders.

Methods

The primary methods used by investigators in this Branch are PET (positron emission tomography) and NMR (nuclear magnetic resonance). New PET radiotracers are synthesized for use as in vivo ligands to measure many different molecular targets, including membrane-bound receptors, proteins associated with intracellular signal transduction, and ones that reflect gene expression. Several NMR methods are also studied to measure molecular targets (magnetic resonance spectroscopy (MRS)), local neuronal activity (functional MRI (fMRI)), and brain structure (structural MRI).

Components

This Branch has three sections, each headed by a tenured scientist:

• Section on PET Neuroimaging Sciences: Chief, Robert Innis, MD, PhD
• Section on PET Radiopharmaceutical Sciences: Chief, Victor Pike, PhD
• Section on Magnetic Resonance Spectroscopy: Chief, Jun Shen, PhD

Brief Overview

The first two Sections on Radiopharmaceuticals and Neuroimaging are almost exclusively oriented to PET. These two sections include a strong methodological orientation, with state-of-the-art facilities to develop, evaluate, and then apply new radiotracers for in vivo imaging. New radiotracers are synthesized and then rigorously evaluated in animals (rodents and primates) to assess their utility for localizing, quantifying, and measuring the functional status of their targets. Promising candidate radiotracers are extended to human subjects, first in healthy subjects and then in relevant patient populations.

The Neuroimaging Section applies both PET and NMR imaging technologies to investigate the neurobiological bases of neuropsychiatric disorders. Because different imaging technologies have distinct capabilities, strengths, and limitations, studies are designed so that the same subjects are iteratively studied using multiple techniques to provide complementary information about pathophysiology.

The Section on Magnetic Resonance Spectroscopy (MRS) develops and applies both high-resolution and in vivo MRS and imaging techniques. In vivo MRS is a method for non-invasive assessment of the homeostasis and dynamics of important endogenous, metabolically active compounds and neurotransmitters in the brain. This Section develops and applies both high-resolution and in vivo MRS and imaging techniques. Working with high-field magnetic resonance spectrometers, this Section develops novel NMR methods and applies them to the study of neurotransmission and neurometabolism, with significant opportunities available for multi-modal collaborative imaging using MRS, MRI, and PET.

Facilities

PET Radiochemistry Facility

The NIMH PET radiochemistry facility is directed by Victor Pike, PhD. This laboratory is fully equipped for radiochemistry research and development as well as production of PET radiopharmaceuticals for imaging studies. The laboratory contains six hot-cells, each connected to two cyclotrons capable of producing both carbon-11 and fluorine-18. The hot-cells are equipped with a variety of commercial automated synthesis equipment including GE TRACERlab FX N and FX C systems, Bioscan AutoLoop, and Advion Nanotek microfluidic system, as well as several systems that have been developed in-house. The laboratory is also equipped with four fume hoods for medicinal chemistry and supporting analytical equipment, including several HPLCs, LC-MS, GC-MS, and 400 MHz NMR.

NIMH also has the use of four hot-cells and two mini-cells in the adjoining cGMP facility operated by the NIH Clinical Center . This facility is equipped with automated synthesis equipment and HPLC, and used exclusively to produce PET radiopharmaceuticals for clinical studies.

PET Imaging

The NIH PET Department has two Siemens Biograph mCT PET cameras and a Siemens High Resolution Research Tomograph. The branch receives a full range of support, from personnel to equipment, from the NIH Clinical Center . In addition, NIMH has two preclinical PET scanners: a Siemens microPET Focus 220 for nonhuman primate imaging and a Focus 120 for rodent imaging.

MR Imaging

Most MRI/fMRI studies are carried out on the 3 and 7 Tesla magnets at the Functional Magnetic Resonance Imaging Core Facility or Clinical Center Radiology Department. In addition, 9.4 and 7 Tesla small animal MR scanners are available at the NIH MRI Research Facility/Mouse Imaging Facility  (NMRF/MIF), a shared intramural resource for animal imaging studies.