MR Technologies and Techniques

Yale offers state-of-the-art neuroimaging capabilities with three Siemens Prisma 3T scanners and one wide-bore Siemens Vida 3T scanner. In addition, we have extensive peripherals to complement our scanners, including MR-compatible eye-tracking, psychological monitoring, and EEG.

Multimodal neuroimaging

• Expertise in diffusion-weighted, structural, and functional MRI
• Two EyeLink 1000 Plus eye-tracking systems
• Psychological recording via BIOPAC
• 8-, 32-, and 64-channel head coils
• Private behavioral testing and interview rooms
• Blood collection space
• MR-compatible EEG systems
• Ambient and refrigerated multi-speed centrifuges, hematocrit, and HbA1C analyzers

Early life neuroimaging

• Flexible body coils and wide bore scanners for fetal neuroimaging
• Physiological monitoring equipment to monitor infants
• Mock scanner to assist with scanning children

Neuroimaging in large animal models

• Veterinarian support to anesthetize, intubate, and monitor animals during scanning
• Variety of head coils to support different skull sizes
• Wireless physiological monitoring equipment to monitor the animal from the control room
• Examples: Non-human primate (fetuses, infants, juveniles, adults), canines, armadillos

Real-time functional MRI neurofeedback

• Online motion correction
• Real-time activation and connectivity processing
• High-memory and GPU-equipped workstations

Pharmacological neuroimaging

• Four individual hospital beds, separated by a wall or a curtain.
• Intravenous glucose tolerance tests, clamps, and infusions.
• oxygen and suction capability

Body imaging capabilities at Yale span several organ systems and characterization strategies. Extensive peripheral equipment complements the high-end capabilities of our scanners.

Cardiovascular imaging

• Characterize LV, RV, and LA function with 2D cine, for volumes, ejection fractions, and diastolic parameters
• Characterize myocardial tissue using T1, T2 and T2* mapping
• Quantify valvular regurgitation based on flow and cine.
• Measure flow in the major arteries with 2D and 4D flow
• Visualize aortic vessel wall and characterize pulse wave velocity in aorta or carotids.
• Perform BOLD imaging (T2* mapping) during cuff-induced ischemia of the legs/arms
• With gadolinium contrast:
• Measure myocardial perfusion. Late gadolinium enhancement and extracellular volume fraction
• Perform contrast MR angiography from the carotids to the feet.
• Able to visualize arteries with non-contrast approaches.
• Have dedicated cardiac coils, peripheral coils, and body coils.

Prostate imaging

• Accelerated T2w and diffusion-weighted imaging of the prostate
• Ultrahigh diffusion weighting possible with unique gradient hardware
• Advanced diffusion analysis and modeling
  • Diffusion tensor imaging for directional analysis (tractography, anisotropy, etc.)
  • Time-dependent diffusion imaging that models fiber/cell sizes and permeability
• Quantitative mapping of T2 and ADC

Skeletal and Body Composition Imaging

• Fat/water quantification in abdomen or extremities (e.g. hands)
• Advanced diffusion analysis and modeling
  • Diffusion tensor imaging for directional analysis (tractography, anisotropy, etc)
  • Time-dependent diffusion imaging to model fiber/cell sizes and permeability
• Quantitative mapping of T2 and ADC

Liver imaging

• Breath hold and respiratory-gated scans
• T2* mapping for iron overload
• T2 mapping for fibrosis or edema
• Quantitative assessment of fat fraction (e.g., for NAFLD)
• Diffusion-weighted imaging
• DCE and VIBE (during contrast)

Monitoring available for post-processing or gating

• Respiratory bellows and Navigator-gating
• Peripheral-gating and ECG-gating

MRS studies at Yale Imaging are primarily focused on the detection of metabolite levels and metabolic fluxes in humans and animals. Signals are obtained from localized volumes in metabolically active tissues like brain, liver, muscle or heart. MRS can be applied across a range of diseases and conditions including cancer, diabetes, aging and addiction. Human studies are performed at clinical magnetic field strengths (3 – 4T), whereas animal studies can benefit from ultrahigh magnetic fields (9.4 – 11.7T). In addition to direct in vivo studies, Yale Imaging has high-resolution NMR systems for in vitro studies of bodily fluids (blood, urine, CSF) and tissue extracts. We offer standard MRS methods and state-of-the-art, advanced MRS methods. Unless noted otherwise, similar methods are available on the human 4T and animal 9.4T and 11.7T systems.

Standard (routine)

Standard MRS methods are those that are routinely used within the MRRC, require no or minimal development, and come with routine processing methods (i.e., LCModel). Standard MRS methods are primarily focused on detecting metabolite ratios/concentrations and include:

• Water/lipid composition (liver, muscle)
• Single-voxel, long-TE ¹H MRS (NAA, tCho, tCr, water)
• Single-voxel, short-TE ¹H MRS (Glu, Gln, mI) with optional macromolecule nulling.
• Single-voxel, edited ¹H MRS (GABA, GSH, 2HG, BHB, Lac)
• ¹³C MRS of muscle and liver glycogen with ¹H decoupling and nOe.

Advanced (development)

Advanced MRS methods are those that are available within the MRRC but require substantial development to tailor the method to the specific application. Any study that involves administration of isotopically enriched substrates (²H, ¹³C) is automatically labeled as advanced. Development is not only limited to the MRS acquisition methods but may also require substantial development of post-processing routines. Advanced methods are primarily focused on (1) detection of dynamic metabolism (i.e., fluxes) or (2) detection of metabolic images via MR spectroscopic imaging and include:

• Dynamic ¹³C MRS in combination with oral or IV administration of ¹³C-enriched substrates. ¹³C MR methods can include ¹³C pulse-acquire, ¹H-¹³C polarization transfer, nuclear Overhauser enhancement, ¹H decoupling and spatial localization. Typical detection targets are ¹³C-labeled Glu, Gln, GABA and Lac, providing information of dynamic metabolic rates of glycolysis, TCA cycle, and neurotransmission.
• ¹H-detected ¹³C MRS (POCE) gives similar results as 2A at a higher sensitivity but comes with greater technical complexity.
• ¹³C-based studies provide detailed spectroscopic characterization of multiple metabolic pathways in parallel. However, ¹³C MRS does not have sufficient sensitivity to allow metabolic imaging. The low spectroscopic information content of deuterium (²H)-based MRS is offset by enhanced sensitivity and reduced technical complexity, thereby allowing 3D deuterium metabolic imaging (DMI).
• Parallel detection of proton-based MRI/MRS(I) and X-nucleus-based through interleaved acquisition strategies offers the time-efficient detection of complementary anatomical, functional, and metabolic information. This approach is the default acquisition strategy for MRI and DMI on the human brain and presents an ideal platform for time-limited and patient studies. A 45-minute scan session can provide a complete 3D DMI dataset, in addition to multi-contrast MRIs like T₁-weighted MP-RAGE, FLAIR, T_2, and susceptibility-weighted MRI.
• MRS of single volumes is relatively routine due to high-quality localization methods and adequate magnetic field homogeneity. MR spectroscopic imaging (MRSI) offers the advantage of detecting spectroscopic signals from extended regions, but is still considered an advanced method due to challenges in localization and magnetic field homogeneity. The Yale MRRC has developed unique hardware that addresses both challenges; A 54-channel multi-coil shim array (MCA) provides unprecedented magnetic field homogeneity far exceeding that achievable with standard shimming hardware. A 3-channel second-order gradient coil to achieve elliptical localization with pulsed second-order field (ECLIPSE) provides high-quality elliptical localization with minimal RF power requirements. The combination of MCA-ECLIPSE can be used to achieve non-elliptical localization. MRSI in combination with MCA-ECLIPSE achieves spectroscopic signal detection across large regions of interest with a quality that is on par with single-volume MRS. MCA shimming hardware is available on the animal scanners, whereas ECLIPSE for rodent brain is under development.
• Phosphorus (³¹P) MRS is another commonly employed method to study energy metabolism in vivo. Static ³¹P MRS gives information on phosphomono and diesters (PME, PDE), phosphocreatine and ATP, as well as intracellular pH and [Mg²⁺]. Dynamic ³¹P MRS with in-bore muscle stimulation allows detection of PCr recovery rates, whereas dynamic ³¹P MRS with selective saturation of resonances allows detection of PCr and ATP synthesis rates.

High-resolution NMR (500 MHz)

A wide variety of high-resolution, liquid-state studies can be performed on our 500 MHz Bruker system. ¹H and X-optimized 5 mm probes are available, equipped with single or triple-axes gradients. Shimming is available up to the sixth order, routinely providing linewidth below 1 Hz. A wide range of 1D and 2D experiments with full temperature control are available, including ¹H-[¹³C] NMR, 2D HSQC, and diffusion-weighted MRS.

MR coils – human 4T

• Proton (¹H) volume head coils (adult human brain)
  • TEM coil
  • Open quadrature coil
  • 16-channel Tx/Tx coil
• Surface coils
  • ¹H surface coil (~100 mm diameter) with quadrature ¹³C half coil (brain)
  • ²H surface coil (~100 mm diameter) with quadrature ¹H half coil (liver)
  • ¹³C surface coil (~100 mm diameter) with quadrature ¹H half coil (brain)
  • ³¹P surface coil (~100 mm diameter) with quadrature ¹H half coil (brain)
• Advanced coils
  • 8-channel ¹H Rx + 8 channel ²H Rx + quadrature birdcage ¹H/²H Tx (brain)
  • 8-channel ¹H Tx/Rx coil combined with 54 multi-coil setup (advanced shimming) and 3 coil ECLIPSE setup (for advanced localization) (brain)

MR coils – animal systems

• Cryoprobes (surface coils for brain, summer 2025)
  • Proton cryoreceive with volume coil transmit.
  • Deuterium cryo-transreceiver with local proton transceiver.
  • Sodium cryo-transreceiver with local proton transceiver.
• Proton (¹H) volume head coils (rodent brain)
  • Volume coil with surface coil receive.
  • ¹H/²H volume coil (50 mm diameter).
• Surface coils
  • Multiple ¹H surface coils (~15 mm diameter).
  • Multiple ¹H-X surface coils (~15 mm diameter) with X = ²H, ¹³C, ²³Na or ³¹P.