Magnetic Resonance Imaging (MRI)

MRI allows for in vivo imaging studies for humans and animals. In addition to the conventional anatomical imaging methods, the Penn State College of Medicine MRI Core provides the following MRI modalities for advanced research:

• Functional MRI
• Quantitative parametric mapping
• Quantitative morphological measurement
• Diffusion imaging
• Tractography
• Magnetic resonance spectroscopy

Functional MRI (fMRI)

Functional MRI is used to examine brain functions or activations. The active areas of the brain for specific tasks will show enhancement from the increased oxygen in those areas of the brain. A given brain activation map can be elicited with a task paradigm designed by the researchers.

Functional MRI requires post-processing techniques after MRI data are collected.

Quantitative Parametric Mapping (qMRI)

Quantitative parametric mapping uses MRI parameters to quantify the associated pathological changes such as tissue iron concentration, edema, cortical thickness or atrophy.

Quantitative Morphological Measurement

MRI provides versatile and superior contrasts (T1 and T2) between various tissues. For example, T1 can be used to locate tumors in the brain in vivo or to observe changes in the abdominal fat pad, while T2 can be used to examine bone regeneration and hydrocephalus regions in the brain.

Diffusion Imaging

Diffusion weighted imaging contrast is based on the rate of water diffusion in the tissue described by a parameter called apparent diffusion constant. It is used for evaluation of stroke and many other diseases. Areas which are injured during a stroke show up darker on an apparent diffusion constant map than healthy tissue does.

Diffusion tensor imaging is used to map the anisotropy of the water diffusion in the tissues. This provides a powerful tool to visualize the brain white-matter tracts and to assess the changes due to diseases or trauma. Fractional anisotropy is used to characterize the diffusion tensor imaging changes.

Tractography

Tractography is used to examine the white-matter tracts and the changes associated with brain diseases with diffusion tensor imaging. It is also used for studies of the brain activation network.

Magnetic Resonance Spectroscopy

Magnetic resonance spectroscopy is used to study neurochemicals and their changes due to diseases in a tissue with NMR spectrum in vivo.

Metabolites

Equipment

The MRI Core has two MRI systems and an EEG MRI-compatible system dedicated for research.

• 3T Siemens PRISMA-Fit scanner equipped with True 2 Channel Tx and 128 Channel Rx
• The latest RF coil set including a 64-channel head coil and software packages with full clinical capability
• 7T Biospec 70/20as small-animal imaging system (Bruker Biospin, Ettlingen, Germany)
• 128-channel high density geodesic MRI-compatible EEG system
• Full sensory fMRI stimulation systems
  • SenSaVue System for visual and auditory stimulation (Invivo Corp, Florida), which includes an LCD visual display, audio system, button response unit and software (E-Prime) for paradigm creation, patient management, protocol planning, precise delivery of brain stimulation and behavioral analysis
  • ETT olfactometer with full-programmable six independent channels for odor and trigeminal stimulation (ETT, Hershey, Pennsylvania)
  • Olfact Smell Test System (Osmic Enterprises, Cincinnati, Ohio), a computerized instrument to test the smell functions of human subjects; functions that can be tested are odor threshold, odor identification and odor memory
  • ETT gustatometer with full-programmable seven independent channels for taste stimulation (ETT, Hershey, Pennsylvania)
  • Eye Link 1000 Plus Host PC system via SR Research: Performs real-time eye tracking at 250, 500, 1000 or 2000 samples per second while computing true gaze position on the display viewed by the participant
    • Host PC also performs online detection and analysis of eye-motion events such as saccades, blinks and fixations
    • In addition to sample data, events are stored in data file on host PC and can be sent through the ethernet link to the display PC with a minimal delay, or output as analog signals
    • From host PC, operator performs participant setup, monitors performance and can communicate with applications running on display PC

Additionally, the facility also has an Agilent E4991A RF Impedance material analyzer, an HP 4195A Network Analyzer, an HP 8452A Diode Array Spectrophotometer, an Orion EA920 pH/ion analyzer, balances, a LeCroy 9450A 300 MHz dual digital oscilloscope, two analog oscilloscopes, two Morris Model 505 RF Sweepers and an HP 4263A LCR Meter.

The following information may be used in grant submissions or to orient investigators to other support available for research at the College of Medicine.

3-D Printer via Form Labs

This instrument is used for prototyping parts and customized devices of MRI peripherals requested by researchers.

Animal Capabilities

The Animal Resource Facility includes central animal quarters in the Medical Sciences Building. The unit features an experimental surgery area, holding area for most species, and full radiological, histopathological, chemical and microbiological supports.

Computational Power

The MRI core includes a 32-processor (3.0 GHz) cluster with 16 GB RAM and 1830 GB RAID storage, eight Dell multiprocessor workstations with an array of software packages for image processing and electromagnetic field calculations, a large-format Mitsubishi dye sublimation printer and an Opal digital slide maker.

Shops

The medical center is equipped with machine and electronic shops that are available for projects and operate on about a one-week turnaround.

To use MRI facilities for research or clinical trials, users must first submit a protocol via iLab.

The application requires basic information to be completed, as well as the submission of an abstract and relevant consent forms or letters of approval.

The abstract should clearly and concisely describe aims and hypotheses, background and significance and the experimental plan, and include sufficient detail to allow for evaluation on scientific merit.

Any materials or equipment that an investigator proposes to take into the magnet area must be described as part of the application.

Upon receipt of the application, the Protocol Review Committee will evaluate the feasibility and safety.

The Protocol Review Committee holds overall responsibility for scientific quality and safety assurances for the project.

Following review, each protocol will be considered:

• approved;
• approved pending revisions;
• not approved; or
• deferred.

Protocols approved pending revision must be resubmitted to the chair of the Protocol Review Committee, who is able to approve the revisions without convening the entire committee. Deferred protocols must be resubmitted to the committee with additional information appended.

Investigators may be invited to clarify their protocol to the committee. Their presence is not required unless requested for these committee meetings.

It is the responsibility of investigators to follow strictly all guidelines established for conducting research in the MRI Core including the maintenance of logs for all systems and the filing of screening forms, informed consent forms and exit questionnaires where applicable for human participants.

All publications, press releases or other documents that result from the utilization of any Penn State College of Medicine Institutional Research Resources, including funding, tools, services or support, are required to credit the core facility and associated RRID.

“The MRI Core (RRID:SCR_021198) services and instruments used in this project were funded, in part by the Pennsylvania State University College of Medicine via the Office of the Vice Dean of Research and Graduate Students and the Pennsylvania Department of Health using Tobacco Settlement Funds (CURE). The content is solely the responsibility of the authors and does not necessarily represent the official views of the university or College of Medicine. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations, or conclusions.”

The following boilerplate language can be used in grant applications when referencing the College of Medicine MRI Core.

MRI Core

Penn State College of Medicine’s MRI Core has 3,000 square feet of laboratory space, which includes biochemical, mechanical, electronic small-animal handling and surgical suits and a fully equipped machine shop with CNC. The CNC CM-1 Compact Mill is a small-footprint, high-accuracy solution for producing and prototyping small, high-precision 2D and 3D parts.

Equipment

The College of Medicine MRI Core has two MRI systems dedicated for research.

• 3T Siemens PRISMA-Fit scanner with a bore size of 60 cm equipped with True 2 Channel Tx and 64 Channel Rx. This can be used for human and large-animal MRI studies. The latest RF coil set includes 16 coils (e.g., Siemens 20- and 64-channel head and neck receive coils, and knee, elbow, liver, etc. coils) and software packages with full clinical capability, which can provide high-SNR images of the whole body.
• 7T Biospec 70/20as small-animal imaging system with a bore size of 20 cm (Bruker Biospin, Ettlingen, Germany), equipped with the latest hardware and software (Avance NEO with Paravision 360).

The core also has multi-sensory fMRI stimulation and monitoring systems:

• Nordic Neuro Lab (NNL) and Current Designs Birch Optical Interface Unit which includes an MRI-compatible LCD visual display (NNL), audio system, several button response units (Current Designs) and software (E-Prime) for creating experiments, patient management, protocol planning, precise delivery of stimuli, and behavioral analysis.
• ETT Olfactometer features an easy-to-use, interactive interface software solution. The Olfactometer connects to an odorant carrier that can hold up to 6 different odorants. Experiments can be programmed and saved to a computer. Stimulus delivery can be sequential or simultaneous and can be set to either monorhinal or dirhinal. Respiration can be monitored and recorded. Additionally, odorant delivery can be triggered by respiration or MRI-TTL pulses. This makes it convenient to simultaneously run visual prompts and record feedback. The Olfactometer can run independently or be paired with fMRI studies.
• The Olfact Smell Test System (Osmic Enterprises Inc., Cincinnati, Ohio) is a computerized instrument to test the smell functions of human subjects. The smell functions that can be tested are odor threshold, odor identification and odor memory.
• ETT Gustatometer with seven fully programmable independent channels for taste stimulation (ETT LLC, Hershey, Pa.).
• Eye Link 1000 Plus system via SR Research. The Eye-Link 1000 Plus Host PC performs real-time eye tracking at 250, 500, 1,000 or 2,000 samples per second while computing true gaze position on the display viewed by the participant. The Host PC also performs online detection and analysis of eye-motion events such as saccades, blinks and fixations. In addition to the sample data, these events are stored in a data file on the Host PC. They can be sent through the Ethernet link to the Display PC with a minimal delay or output as analog signals (if the optional analog/digital I/O card is installed). From the Host PC, the operator performs participant setup, monitors their performance and can communicate with applications running on a Display PC.
• Olfactory Threshold and Identification devices (Osmic Enterprises Inc.). The OLFACT family of instruments delivers computerized, self-administered tests for assessing odor thresholds, odor identification and odor memory. The tests are currently being used by physicians, researchers and commercial businesses to test for anosmia, hyposmia and many aspects of normal olfactory function. Additionally, the tests are being used to evaluate personal preferences for various fragrances, odor interactions/masking and the relationship between taste and smell. Scientists are also discovering unique relationships between neurodegenerative diseases like Alzheimer’s and Parkinson’s diseases and the sense of smell.
• Patient Monitoring System/Philips MR400 MRI Compatible. SPO2, ECG, NIBP, Pulse and ECG recordings.
• BioPac wired and wearable wireless physiology measurement and interpretation solutions. The main hardware and software are the 16-channel data acquisition system and the MP160WSW EDA100C-MRI amplifier used for electrodermal activity. The INISO-TRIGA: TTL Trigger Isolation Adapter is ideal for recording trigger signals produced by MRI scanners. The NIBP-MRI is a wireless and noninvasive physiological monitoring system that tracks blood pressure, using pulse-decomposition analysis technology as well as heart rate. The PPG100C “Photo Plethysmogram Amplifier” adapter is for recording the pulse pressure wave and provides an indication of blood pressure, blood density or vasoconstriction. Front panel controls allow selection of either absolute or relative plethysmographic measurements.

The core also has an Agilent E4991A RF impedance material analyzer, an HP 4195A network analyzer, an HP 8452A diode array spectrophotometer, an Orion EA920 pH/ion analyzer, balances, a LeCroy 9450A 300 MHz dual digital oscilloscope, two analog oscilloscopes, two Morris Model 505 RF sweepers and an HP 4263A LCR meter.

The core has (2) options available for 3-D printing. 1. Form Labs is being used for prototyping parts and customized devices of MRI peripherals requested by researchers. 2. Fusion3 High Performance 3D (F410 3D Printer) via Fusion3 Design LLC.

Animal Capabilities

The Animal Resource Facility includes central animal quarters, the Animal Research Farm and a large dairy farm. The unit features an experimental surgery area, holding area for most species and full radiological, histopathological, chemical and microbiological supports, as well as an on-site 187-square-foot vivarium with clean room preparation.

Computational

The MRI Core includes:

• 16-core server (i9-7960X) with 64 GB RAM, two NVidia Titan V GPUs (12 GB VRAM each) and 10 TB RAID storage
• 16-core server (Xeon Gold 6242) with 96 GB RAM, two NVidia Quadro GV100 GPUs (32 GB VRAM each) and 20 TB RAID storage
• Three Dell multiprocessor workstations with an array of software packages for image processing and electromagnetic field calculations
• A dedicated research PACS system with 11 TB storage and fiber optics network for real-time image data access and distribution to each individual investigator’s personal data folder

Other

The Penn State Health Milton S. Hershey Medical Center is equipped with both machine and electronic shops that are fully available for projects and operate on about a one-week turnaround.

Additional information on the following systems:

OLFAC Smell Test System: The Olfac Smell Test System (Osmic Enterprises, Inc., Cincinnati, OH) is a computerized instrument to test the smell functions of human subjects. The smell functions that can be tested are odor threshold, odor identification, and odor memory. The odor threshold test measures a person’s ability to detect an odor. Thirteen concentrations of an industry standard odorant are used. The participant smells two samples, one blank and one with an odorant. They are then asked to determine which of the two samples is the stronger. The concentrations are decreased or increased depending on whether the stimulus is identified correctly. The Odor Identification Test tests a person’s ability to identify a series of twenty different odors. During the test, after smell the odor, the subject s selects the correct odor from four choices on a computer screen. The Odor Memory Test assesses a person’s ability to remember the odors that were presented earlier. The test begins with a presentation of ten odors. After a 10-minute break, twenty odors will be presented, including the ten original odors. The subjects need to identify the odor and if it is a new odor. A tutorial is built into the program so the subjects can easily learn the task procedures.

ETT Olfactometer: The ETT Olfactometer (Emerging Tech Trans, LLC.) is a computerized instrument for odor delivery. It’s MRI compatible and features an easy-to-use, interactive interface with touchscreen control. Its odorant carrier can hold up to six different odorants or six different concentrations of the same odorant. Odor delivery paradigms can be programmed to be sequential, simultaneous, monorhinal, or birhinal, and can be saved to the Olfactometer directly, or in a separate control computer. The execution of the odor delivery paradigm can be synchronized with functional data acquisition (e.g., fMRI and EEG) and the execution of instructions, other task or stimulation paradigms. The subject’s respiration activity and subjective response can be monitored and recorded. The odor delivery can also be triggered by the respiration activity.

ETT Gustatometer: The ETT Gustatometer (Emerging Tech Trans, LLC.) is a computerized instrument for taste delivery. It’s MRI compatible. It hosts eight channels, each with an input and output port. The execution of the taste delivery paradigm can be synchronized with functional data acquisition (e.g., fMRI and EEG) and the execution of instructions, other task or stimulation paradigms.

For current scanner rates and data analysis fees, contact Research Project Manager Jeff Vesek at jvesek@pennstatehealth.psu.edu.

Scanner usage charges will be calculated following the reserved time slot in the scanner scheduling system or the time actually used, whichever is larger. Data analysis fees are charged for things including but not limited to FMRI, DTI, MRS, volumetric and morphologic data processes.

Payment will be due upon receipt of the invoice.

In case of the inadequate quality of data collected due to MRI system problems, the scanner charge will be waived.

The center will not be responsible for the inadequate data quality due to the experimental design, execution of the experiment, subject movement and statistical errors.

In case of cancellations due to unforeseeable events, it is the user’s responsibility to notify administrators at least 48 hours in advance to reschedule the study time, as follows:

• For Siemens 3T, contact Jeff Vesek at 717-531-0003, ext. 285782 or jvesek@pennstatehealth.psu.edu.
• For Bruker 7T, contact contact Jian-Li Wang at jxw73@psu.edu.

Otherwise, the usage will be charged as scheduled.

Investigators will be provided with information on procedures of booking the scanner time for proposed studies after their information is reviewed by the Protocol Review Committee.