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imaging facilities

The Center for In Vivo Microscopy (CIVM) has numerous imaging systems, unique animal support and monitoring capabilities, visualization tools, and a computer network that all contribute to our world-class facility. Since small animal imaging is so specialized, our integrated team has the skills to design and in some cases, manufacture the equipment needed. Since 1986, CIVM has developed into one of the most comprehensive small-animal imaging facilities in the world. We invite other researchers to set up a collaboration or service project to benefit their research.

MAGNETIC RESONANCE (MR) IMAGING

Our MR imaging systems are unique for small animal imaging, using specially designed magnets and gradients interfaced to state-of-the-art clinical imaging consoles.


1T Aspect MR imager
MR system based on permanent magnets
MR histology images of an actively stained Sprague-Dawley rat. Shown is every 4th slice from a 3D array (spatial resolution of 100 x 100 x 300 microns with acquisition time of about 1 hr).
  • Complements our higher-field systems allowing us to look at phenomena where lower field has advantages, or where field-dependence is important (for example, cryo coils, shorter T1 and longer T2 at lower fields, and hyperpolarized 11C and 15N)
  • Includes a permanent magnet and a compact, totally digital imaging console
  • 500 mT/m gradients have virtually no eddy currents
1.0T Aspect magnet and console


2T MR
For in vivo rat/mouse imaging studies using hyperpolarized gases
2T
  • Oxford 30-cm horizontal medium-bore magnet
  • Controlled by a GE console adapted specifically for MR microscopy
  • Dedicated to pulmonary imaging, but also adapted for other types of studies
  • Hyperpolarization is provided externally, so the strength of the magnet does not affect the signal (to 1st order). Since decay of the signal from the hyperpolarized gas is dominated by susceptibility-induced losses, the lower magnetic field is preferable.
  • 2 sets of gradients, one at 150 mT/m with a 150-mm clear bore, and a 2nd 120 mm that provides 400 mT/m
Figure of a pre-Methocholine drug-induced challenge of an ovalbumin-sensitized mouse, imaged on the 2T MR with hyperpolarized 3He.

Adapted from NN Mistry, A Thomas, SS Kaushik, GA Johnson, B Driehuys, Quantitative analysis of hyperpolarized 3He ventilation changes in mice challenged with Methacholine, Magn Reson Med 63:658–666, 2010, Free PMC article

2Tlung

7T MR
For magnetic resonance histology studies
7T

  • 7.0 T 220-mm Magnex horizontal bore magnet
  • Agilent Direct Drive console features a 14-bit 80 MHz ADC providing an effective dynamic range of 20 bits, particularly relevant to 3D imaging at microscopic resolution
  • Resonance Research shielded gradients (115-mm ID) provide rapid switching to 770 mT/m over an 80 x 100-mm field of view
  • Agilent Direct Drive console
    • 2 independent transmit channels and 4 independent receive channels
    • 14-bit 80 MHz ADC provides an effective dynamic range of 20 bits, important for 3D imaging at microscopic resolution
 

7TcolorFA

Color fractional anisotropy (FA) image of a canine brain with isotropic resolution of 100 microns, acquired on the 7T system.
7.0 T Magnex magnet with Agilent Direct Drive console
   

7T - Bruker
MR system with cryo probe for increased sensitivity
7TBruker

 

  • Smaller bore (200 mm) dedicated to in vivo MR microscopy
  • Features a 70/200 USH small-footprint
  • 2 sets of high-performance gradients. The cryo probe fits into a 116-mm ID gradient, which supplies 450 mT/m with a rise time of 110 micro-seconds
  • 60 shim provides gradients to 1000 mT/m
  • Avance II digital console with dual transmit channels and a 4-channel receiver for phased array coils

Gradient recalled echo image of a live mouse with isotropic spatial resolution at 50 microns. The high signal to noise was obtained by opening the blood brain barrier with BOMUS, to permit infusion of contrast agent. The BOMUS technique was developed at the CIVM (see G Howles et al., Magn Reson Med 2010 PMCID: PMC2950102) and G Howles et al. Neuroimage 2010 PMCID: PMC2859893

bruker7TmouseBOMUS

7T Bruker
We work closely with the Warren S. Warren (Chemistry) lab
7T Burker-Warren
The 7T Bruker magnet in the Warren lab in the Bryan Research Building is used for imaging and spectroscopy of protons, carbon, and nitrogen.
  • A Bruker 7.0T/210 MR system is dedicated to novel contrast mechanisms (e.g. multiple quantum effects) and spectroscopy. The Oxford Hypersense Polarizer is located in the same room, <10 feet from the shielded magnet.
  • CIVM and the Warren lab and have a 3.35 T Hypersense (Oxford Instruments) hyperpolarizer capable of polarizing 13C up to 40% and 15N up to 10% polarization. The model at CIVM has a custom-built 15N probe, which makes it one of the few Hypersense machines capable of performing dissolution DNP on nitrogen.
  • For applications such as molecular and functional imaging of preclinical in vivo cancer models

9.4 T
Small specimens, such as mouse or rat brains, kidneys, and embryos
9T


jiang9T

Color fractional anisotropy (FA) image of an actively stained mouse brain with isotropic resolution of 43 microns.

  • 9.4 T/89-mm Oxford vertical bore magnet
  • Agilent Direct Drive console
  • 2 sets of shielded coils provide switched gradients at 950 mT/m with rise times of <100 micro-seconds
  • Multi-gradient protocols have been developed for susceptibility imaging
  • Spatial resolution below 10 microns has been attained

microCT MICRO-CT / MICRO X-RAY

     Dual energy micro-CT, and dynamic imaging for cardiac and perfusion studies

Components of the dual tube/detector micro-CT system in a rotating specimen geometry:
  • X-ray tubes and detectors are arranged orthogonally
  • 2 Varian G297 x-ray tubes (fs=0.3/0.8 mm)
  • 2 Epsilon High Frequency X-ray generators (EMD Technologies)
  • 2 XDI-VHR CCD x-ray detectors (Photonic Science) with a Gd2O2S phosphor and 22-micron pixel size
  • A geometric calibration method for the dual tube/detector system allows 2-times faster imaging and combinations of projections from the 2 detectors in a single reconstruction
This equipment is also used as a biplane digital subtraction angiography (DSA) system for small animal coronary angiography.

microCT
 
This figure shows images of a C57BL/6J mouse.
CT cardiac (A) Micro-CT images during 12 phases of the cardiac cycle at temporal resolution of 10 ms. (B) Coronal slice at diastole. Isotropic spatial resolution is 88 microns. (C) 4D data permits semi-automated measure of cardiac function based on the volume of the left ventricle.

Adapted from: CT Badea, M Drangova, DW Holdsworth, GA Johnson, In vivo small-animal imaging using micro-CT and digital subtraction angiography, Phys. Med. Biol. 53(19): R319-R350, 2008, Free PMC article


microCT U-SPECT-II/CT

Our newest piece of equipment is being used for cardiac studies: MILabs SPECT-II

USPECT

  • 75 pinholes, 3D focusing technology (ultra-high resolution: <0.35mm in entire mouse, <0.9 mm in entire rat; quantification of molecules in tiny parts of organs; low dose and high-resolution total body imaging)
  • List-mode data acquisition (high number of energy channels (simultaneous multi-isotope imaging; retrospective gating and energy window selection; flexible dose and scan time planning)
  • Stationary detectors for ultra-fast dynamic scanning

Image from a 4D cardiac SPECT study:

  • C57Bl/6 male 25g mouse IV tail vein injection of Tc-99m Myoview
  • 0.35mm high-resolution collimator
  • Scan time: 2 hours
Cardiac SPECT movie

spectmovie


microCT ULTRASOUND

us
  • VisualSonics Vevo 770 Ultrasound system provides real-time ultrasound at spatial resolution down to 30 microns
  • The system includes sophisticated mechanical scanning and 4 probes ranging in frequency from 25 to 40 MHz.
The figure to the right shows how we adapt ultrasound to open the blood-brain barrier (BBB) using unfocused ultrasound and microbubbles for a mouse brain study. The ultrasound and microbubble technique is noninvasive, transcranial, and reversible, and by using an unfocused transducer, this opens the BBB in both hemispheres in a single insonification. This technique uses commercially available components, takes only a few minutes, and requires no expertise in ultrasound.
ultrasoundBOMUS

 

 

This figure adapted from Howles et al. 2010, shows results from the technique that we call BOMUS (BBB Opening with Microbubbles and UltraSound). The MR-7T system was used with Gd- DTPA contrast enhancement.

See our publication about this technique, and another figure with the MR 7T-Bruker description above: GP Howles, KF Bing, Y Qi, SJ Rosenzweig, KR Nightingale, GA Johnson, Contrast-enhanced in vivo magnetic resonance microscopy of the mouse brain enabled by non-invasive opening of the blood-brain barrier with ultrasound, Magn Reson Med, 64(4):995-1004. 2010 PMCID: PMC2950102 


confocal CONFOCAL MICROSCOPE

  • Zeiss LSM 510 META Confocal Microscope with multiphoton capabilities
  • Equipped with several high-performance objectives (including 2 dedicated high-NA, long working distance multiphoton objectives) and numerous filter/detector configurations
  • For tile imaging of large samples, CIVM has added an automated XY stage and macro control software to enable large-volume 2-photon fluorescence imaging in thick cleared brain tissue sections (see figure)

 

confocal

computers COMPUTERS / NETWORK / VISUALIZATION TOOLS

The computational infrastructure is the most critical element in integrating our imaging research and services
  • 5 workflow stages - acquisition, reconstruction, archive, post-processing, analysis, each with dedicated hardware / software
  • 3 linked Oracle databases track and integrate project and specimen details, as well as image data
  • Data available via a secure web tool to our database for users to search, retrieve, and analyze their data interactively from anywhere with a high-speed web connection
  • Dell 10Gb/sec switch to facilitate transfers of large datasets
  • 40 Macintosh workstations for image analysis, most configured with at least 24 GB of memory and a standard set of analysis tools
  • Many of our post-processing pipelines are implemented on a high-end Dell cluster (7 nodes with a total of 224 cores and 2.5 TB of memory), coupled to a 40-TB RAID via a dedicated 10-Gb switch

  • CIVM hosts a NVIDIA GRID server with 6 K2 cards (~ 9000 cores) linked by the 10-Gb switch to the RAID and cluster. The GRID is connected to the outside world by a dedicated 10-Gb connection to the Duke backbone network.
  • Reference atlases have been developed for mouse, rat, Rhesus macaque, and under construction - the human brain stem - see our various publications for detail
  • A recent addition is diffusion MR imaging tractography for a mouse connectome (see our open access Cerebral Cortex article)