Research Tools & Dissemination

Tools

Description

Preclinical

Human Research

Cell, Tissue, Animals

 New Cell 
 & Tissue Culture

DNP/dissolution Methodology & Polarization Hardware

 

Hyperpolarized MRI Toolbox Download

For Preclinical & Human Research: Provides research-level support and prototyping software tools for hyperpolarized MRI experiments. Includes MATLAB code for designing radiofrequency (RF) pulses, readout gradients, and data reconstruction.

Data & File Sharing

For Preclinical & Human Research: National Cancer Institute -IND Regulatory & Manufacturing Resources and examples of in vivo animal and human hyperpolarized MRI data that were acquired with different methods.

 

Videos & Guides for Reconstruction, Analysis & Visualization Tools 

 

 
 

Model Resources

Realistic Preclinical Models and Correlative Science Methods

As part of our TR&D2 project we are proud to offer training in Realistic Preclinical Models and Correlative Science Methods. For more information please fill out our Training Sign-up Form.


Cell, Tissue and Animal Model Resources

Below you will find a list of our Cell, Tissue, and Animal Model Resources. Interested in trying one of our model systems? Email us at [email protected].

Infection Models

Model System

HP Application

HP Probe

Reference


E.Coli, S.Aureus

Bioreactor (alginate encapsulated) and cell slurry

Inflammation

Model System

HP Application

HP Probe

Reference


Macrophages 

Cell slurry 

[1-13C]pyruvate
[1-13C]dehydroascorbate

Non-invasive Detection of M1 Activation in Macrophages using Hyperpolarized 13C MRS of Pyruvate and DHA at 1.457 Tesla. ISMRM Virtual Annual Meeting, August 2020, 0630.

Liver Models

Model System

HP Application

HP Probe

Reference


CCl4 fibrosis

In vivo

[1-13C]pyruvate
13C-Urea

N/A


Zucker Diabetic Fatty (ZDF) diabetes 

In vivo

[1-13C]pyruvate
 

N/A


Methionine Choline Deficient Diet

In vivo

[1-13C]pyruvate
[1-13C]dehydroascorbate

N/A


High fat diet 

In vivo

[1-13C]pyruvate
 

N/A

Wag Rij/CC531 Colorectal cancer metastasis 

In vivo

[1-13C]pyruvate
 

N/A

 

Multiple Sclerosis Models 

Model System

HP Application

HP Probe

Reference



Cuprizone-EAE model

In vivo

[1-13C]pyruvate
13C-Urea

Hyperpolarized 13C MRSI of pyruvate and urea can detect immunomodulatory responses to dimethyl fumarate therapy in a model of multiple sclerosis ISMRM Virtual Annual Meeting, August 2020, 3003.

 

Neuroinflammation

Model System

HP Application

HP Probe

Reference


LPS-induced mouse model of inflammation

In vivo

 

Prostate Cancer Models

Model System

HP Application

HP Probe

Reference


PC3, Du145, LnCaP

Bioreactor (alginate encapsulated) and cell slurry


TRAMP (genetic mouse model), LDHA knockout

In vivo


PDX (LTL and LuCaP series)

Sub-renal, intratibial and intrahepatic 

[1-13C]pyruvate
13C-Urea

N/A


 

Renal Cell Carcinoma Models

Model System

HP Application

HP Probe

Reference


UOK262, UMRC6, HK-2

Bioreactor  (alginate encapsulated) 



PDX

Orthotopic in vivo
Tissue slice culture (bioreactors)

[1-13C]pyruvate

N/A


Traumatic Brain Injury

Model System

HP Application

HP Probe

Reference


Controlled cortical Impact model

In vivo

 

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Bioreactor Resources

As part of our TR&D2 project we are proud to offer training in New Cell & Tissue Culture Bioreactors. For more information please fill out our Training Sign-up Form.

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Production & Development Resources

Preclinical Production & Development Resources

HP Imaging & Production Facility-Virtual Overview:
Click here to learn more about: Our Facility, Team & Support/Offerings

Probe Development for Preclinical Research

Equipment Descriptions:
Oxford PulsarTM Benchtop NMR Spectrometer System 
Ocean Insight DH-2000-BAL Light Source 
Micro-Osmette Automatic High Sensitivity 50 uL Osmometer

Production for Preclinical Research

Equipment Descriptions:
HyperSense DNP Polarizer 
 

Education & Training:
- Dissolution-DNP: Formulation of carbon-13 labeled compounds: 
As part of our TR&D2 project we are proud to offer training in Formulation of Carbon-13 Labeled Compounds for Dissolution-DNP. This document covers the following topics: Glassing and High Compound Concentration; Stability of Compound Formulations; Trityl Radical Storage, Handling, Structures and Molecular Weight; Recipes for: Metabolism Probes, Perfusion Probes, Extracellular pH Probes, Metal Ion Probes, Redox Probes, Necrosis Probes 


Resource: Recipe / Protocol
Format: PDF (Updated 03/05/2020)
Applicable Research Areas: 
Preclinical 

- Probe Preparation Demo: Preparation + QC of Compounds for Hyperpolarization:  As part of our TR&D2 project we are proud to offer a demo in Preparation + QC of Compounds for Hyperpolarization. Click the link to the right to learn more about: Sample set up, Basics of HP Formulation, Quality Assurance of Formulated Agents, Advanced HP Formulation Strategies, Sample Agent Formulation Flow Chart.

Resource: Written Demonstration
Format: PDF (Updated 03/23/2017)
Applicable Research Areas: 
Preclinical 

Sample Methods for HyperSense DNP Polarizer: Methods for Polarizer Set-up

Resource: Method
Coming soon

HP Probe Preparation Training in Novel Hyperpolarized MR molecular Imaging Probes: As part of our TR&D2 project we are proud to offer HP Probe Preparation Training in novel hyperpolarized MR molecular imaging probes. For more information please email [email protected].

Resource: Hands-on Support 
Contact: [email protected]

- Reusable/Research Fluid Path (RFP) Assembly Protocol – A quick reference guide: This is a quick reference guide for investigational and preclinical use only and should not be used for human studies.

Resource: Reference Guide
Format: PDF (Updated 02/01/2021)
Applicable Research Areas: 
Preclinical 

Presentation & Tutorials: 
Preparation and Clinical Translation of 13C MRI Agents (.pdf) and Audio File (.mp4)
Description: This poster presentation given by Dr. Andrew Riselli, PharmD, RPh, HP Research Pharmacist gives an overview of the Preparation Procedures and Clinical Translation Process of three agents at UCSF currently underway: [13C]pyruvate/urea Combination: IND Submitted, [13C]bicarbonate: Nonclinical Studies, [1-13C]α-ketoglutarate (α-KG): Formulation Development. 

 

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Human Research Production & Development Resources

HP Imaging & Production Facility-Virtual Overview:
Click here to learn more about: Our Facility, Team & Support/Offerings

Probe Development for Human Research

Equipment Descriptions:
Ocean Insight DH-2000-BAL Light Source 

Production for Human Research

Equipment Descriptions:
Labconco Purifier 4ft Horizontal Clean Bench and Getinge Isolator

5T GE SPINlab Multisample Polarizer, QC Unit Prototype & Multiprobe QC

Presentation & Tutorials: 
Preparation and Clinical Translation of 13C MRI Agents (.pdf) and Audio File (.mp4)
Description: This poster presentation given by Dr. Andrew Riselli, PharmD, RPh, HP Research Pharmacist gives an overview of the Preparation Procedures and Clinical Translation Process of three agents at UCSF currently underway: [13C]pyruvate/urea Combination: IND Submitted, [13C]bicarbonate: Nonclinical Studies, [1-13C]α-ketoglutarate (α-KG): Formulation Development. 

Production Process of Hyperpolarized Compounds and Terminal Sterilization by Filtration Impact on Patient Safety (.pdf) 
Description: The purpose of this presentation is to evaluate the impact of using terminal sterilization without radiation in the production of sterile products. The approach discussed focuses on the manufacturing process in regards to bacterial contamination and the validation of the effectiveness of a sterility filter in removing bacteria.

- Production Tutorials Videos: Shown below are step-by-step instructional videos on the Production process. Questions regarding these videos? Email this team: [email protected][email protected][email protected]

Education & Training:
- Clinical translation of hyperpolarized 13C
pyruvate and urea (Co-Pol) imaging agents: This presentation given by Dr. Andrew Riselli, PharmD, RPh, HP Research Pharmacist goes over:

  • Developing a formulation and procedure to prepare a sterile HP 13C pyruvate and urea injection product.
  • Conducting nonclinical studies including toxicology. 
  • Submitting the clinical protocol, Chemistry Manufacturing and Controls (CMC), and toxicology reports to the FDA for approval.
  • General guidelines for submitting the clinical protocol to the IRB for approval. 

Resource: Work Flow Presentation
Format: PDF (Updated 08/03/21)
Applicable Research Areas: 
Human Research

- Production of Filled Pharmacy Kits (cassettes) and Terminal Sterilization For Human Studies: As part of our TR&D1 project we are proud to offer training in Production of Filled Pharmacy Kits (cassettes) and Terminal Sterilization For Human Studies. Click on the button to the right to learn more about: Manufacturing Methods & Facilities, Acceptance Testing, Quality Control, Manufacturing and Release, Documentation and Analysis

Resource: Work Flow Presentation
Format: PDF (Updated 11/10/20)
Applicable Research Areas: 
Human Research

- Sample Methods for GE SPINlab Polarizer: Methods for Pharmakit Filling & Polarizer Set-up 

Resource: Methods
Coming soon

- HP Probe Preparation Training in Novel Hyperpolarized MR Molecular Imaging Probes: As part of our TR&D2 project we are proud to offer HP Probe Preparation Training in novel hyperpolarized MR molecular imaging probes.

Resource: Hands-on Support 
Contact: [email protected]

 


Production Facility Support for Human Research:

Presentation: Production Facility for the Preparation of C-13 Hyperpolarized MR Imaging Agents for Human Studies (.pdf) 
Description: The purpose of this presentation is to outline the steps in designing a hyperpolarized stable isotope production facility that meets FDA compliance by following these requirements.

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Polarization Resources

Preclinical Polarization Resources

Equipment Descriptions:
Commercial Oxford Instruments HyperSense 
HyperSense DNP Polarizer 
3.35T GE SPINlab Polarizer 
5T GE SPINlab Multisample Polarizer, QC Unit Prototype & Multiprobe QC
 

Education & Training:
- Overview Hyperpolarized 13C MRI: Polarization Physics & Hardware
:
As part of our TR&D1 project we are proud to offer this seminar lecture on the overview of Polarization Physics & Hardware for Hyperpolarized 13C MRI. Please see the outline below for topics covered. To view the presentation please see the links to the right. 

DNP Physics: Magnetization, Boltzmann Distribution, Signal-to-Noise Ratio, Sensitivity, Thermal Polarization, Brute-Force Polarization, Dynamic Nuclear Polarization, DNP Hyperpolarization, DNP Requirements, Solid Effect, Cross Effect, Thermal Mixing, Spin Diffusion, Effect of Temperature and Field Strength, Effect of Radical

Polarizer Hardware: HyperSense Polarizer (Buildup, Dissolution Procedure, Key Considerations) ; SPINlab Polarizer (Comparison with HyperSense, Fluid Path, Key Considerations, Clinical Applications)

Suggestions on Further Readings

Resource: Slides
Format: PDF or Slides with Audio (Updated: 07/12/19)
Applicable Research Areas: 
Preclinical & Human Research

- Preclinical DNP Polarizer training for improved DNP Methodology: As part of our TR&D1 project we are proud to offer Preclinical DNP Polarizer training for improved DNP Methodology. This training is hands-on which allows users to learn through experience with support from members of our Center. For more information please email [email protected].

Resource: Hands-on Support 
Contact: [email protected]

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Human Research Polarization Resources

Equipment Descriptions:
5T GE SPINlab Multisample Polarizer, QC Unit Prototype & Multiprobe QC
 

Education & Training:
- Overview Hyperpolarized 13C MRI: Polarization Physics & Hardware
:
As part of our TR&D1 project we are proud to offer this seminar lecture on the overview of Polarization Physics & Hardware for Hyperpolarized 13C MRI. Please see the outline below for topics covered. To view the presentation please see the links to the right. 

DNP Physics: Magnetization, Boltzmann Distribution, Signal-to-Noise Ratio, Sensitivity, Thermal Polarization, Brute-Force Polarization, Dynamic Nuclear Polarization, DNP Hyperpolarization, DNP Requirements, Solid Effect, Cross Effect, Thermal Mixing, Spin Diffusion, Effect of Temperature and Field Strength, Effect of Radical

Polarizer Hardware: HyperSense Polarizer (Buildup, Dissolution Procedure, Key Considerations) ; SPINlab Polarizer (Comparison with HyperSense, Fluid Path, Key Considerations, Clinical Applications)

Suggestions on Further Readings

Resource: Slides
Format: PDF or Slides with Audio  (Updated: 07/12/19)
Applicable Research Areas: 
Preclinical & Human Research

- Human DNP Polarizer training for improved DNP Methodology: As part of our TR&D1 project we are proud to offer Human DNP Polarizer training for improved DNP Methodology. This training is hands-on which allows users to learn through experience with support from members of our Center. For more information please email [email protected].

Resource: Hands-on Support 
Contact: [email protected]

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Acquisition Hardware Resources

Preclinical Acquisition Hardware Resources

MR Scanner Coil Development for Preclinical Research

Below you will find a list of our 13C coils for our 3T, 11.7T and 4T systems. Interested in trying our preclinical coil designs? Email us at [email protected].

3T

11.7T

14T


Bruker 1H linear/13C linear mouse body (40 mm)
 

Varian, DD, AutoX DB PFG (5 mm)
nuclei: 13C, 31P, 15N

Varian, M2M Imaging, 1H linear/13C linear (40 mm)
 


Doty 1H linear/13C linear mouse head (20 mm) 

Varian, DD, BB (10 mm)
nuclei: 13C, 31P, 15N

Varian, 13C quad (40 mm) 


Neos Biotec 1H quad/13C quad (45 mm)

Varian, ID, PFG, BB (5 mm) 
nuclei: 13C, 31P, 15N

Varian, BB, DD, 15N-31P(H), AutoX (10 mm)


UCSF 13C quad rat body (76 mm)

Varian, DD, SW/PFG, DB (5 mm)
nuclei: 13C, 31P, 15N; resonance frequency changed from 600 MHz to 500 MHz

 


Pulseteq 13C quad/1H quad (42 mm) 

Varian, gHX Nano, DD
nuclei: 13C, 31P, 15N, 29Si

 


Neos Biotec 13C quad/1H linear (20mm)

Varian, gHX Nano, ID

 

 

Neos Biotec 1H linear/13C linear mouse brain surface 

Varian, DD, BB (10mm)

 

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Human Research Acquisition Hardware Resources

MR Scanner Coil Development for Human Research

Education & Training:
Coil Design: Coil images & descriptions used for Human Research Acquisition - Coming soon. Interested in trying our coil designs for human research? Email us at [email protected].


ResourceDesign Methods
Contact: [email protected]

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Acquisition Software Resources

Preclinical Acquisition Software Resources 

Overview of Pulse Sequences & Acquisition Strategies

MR Acquisition and RF Coils by Dr. Jeremy Gordon: This presentation is an overview of Data Processing provided from the 2019 HP MRI Course and includes topics such as:
- Imaging Trade-offs: T1 Decay, 1H vs 13C Imaging
- Coils & Calibration: RF Coils, Multichannel Arrays, 13C Frequency Calibration, RF Power Calibration, Autonomous Scanning, Flip Angle, Dynamic Imaging
- Imaging Approaches: k-space, HP Imaging of Inert Substrates, SSFP, Metabolically Active Substrates, Dealing with Off-Resonance, Spectroscopic Imaging Techniques, Chemical Shift Imaging, Rapid Spectroscopic Techniques, Model-Based Reconstructions, Signal Model in k-space, Model-Based Reconstructions, Signal Model in k-space, Spectral Selectivity, Slice-Selective Excitation, Spectral-Spatial RF Pulses/Excitation, Metabolite-Specific Imaging, Acquisition Scheme Comparison, Sequence Trade-offs

Resource: Course Presentation
Format: PDF or Slides with Audio  (Updated: 07/26/19)
Applicable Research Areas: 
Preclinical & Human Research

MR Sequences for Preclinical Research

Varian pulse sequence pack: Description coming soon! Interested in learning more about this HP C-13 MR Sequence? Email us at [email protected]

Resource: Sequence Dissemination
Contact: [email protected]

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Human Research Acquisition Software Resources

Overview of Pulse Sequences & Acquisition Strategies

MR Acquisition and RF Coils by Dr. Jeremy Gordon: This presentation is an overview of Data Processing provided from the 2019 HP MRI Course and includes topics such as:
- Imaging Trade-offs: T1 Decay, 1H vs 13C Imaging
- Coils & Calibration: RF Coils, Multichannel Arrays, 13C Frequency Calibration, RF Power Calibration, Autonomous Scanning, Flip Angle, Dynamic Imaging
- Imaging Approaches: k-space, HP Imaging Inert Substrates, SSFP, Metabolically Active Substrates, Dealing with Off-Resonance, Spectroscopic Imaging Techniques, Chemical Shift Imaging, Rapid Spectroscopic Techniques, Model-Based Reconstructions, Signal Model in k-space, Model-Based Reconstructions, Signal Model in k-space, Spectral Selectivity, Slice-Selective Excitation, Spectral-Spatial RF Pulses/Excitation, Metabolite-Specific Imaging, Acquisition Scheme Comparison, Sequence Trade-offs

Resource: Course Presentation
Format: PDF or Slides with Audio  (Updated: 07/26/19)
Applicable Research Areas: 
Preclinical & Human Research

MR Sequences for Human Research

EPI pulse sequence: In order to enable faster, more robust hyperpolarized (HP) MRI for patient studies, we developed a new metabolite-specific broadband EPI pulse sequence for rapid volumetric imaging of HP [1-13C]pyruvate and other molecules. This pulse sequence contains commonly used features such as ramp-sampling, partial-Fourier, and Nyquist ghost correction. It includes built-in spectral-spatial RF pulses and flip angle schemes for pyruvate and other probes, as well as the capability to integrate user-designed pulses and flip angles. This pulse sequence is compatible with clinical MR scanners and includes reconstruction and analysis software, facilitating the integration of metabolic data into the clinical workflow. Please reach out to [email protected] for more information.

MNS Research Pack (GE Healthcare): The MNS Research Pack is a software acquisition package for GE MRI scanners focused on multi-nuclear imaging and spectroscopy for hyperpolarized [1-13C]pyruvate research.  It includes different sequences and semi-automatic pre-scanning. In addition to pre-installed methods, additional RF pulses and trajectories can be designed off-line in Matlab, saved in a file, and read into the sequence. The package is available on request, contact: Rolf.Schulte_at_Research.ge.com

RT Hawk: RThawk is an interactive platform for hyperpolarized [1-13C]pyruvate multislice spiral imaging, providing wide coverage and featuring automatic frequency and power calibrations. Originally developed for cardiac MRI applications, it offers specialized cardiac-gated C13 acquisition techniques integrated into standard proton heart studies, which are tailored for short-axis, long-axis views and more. It also comes with pulse programming environment that allows technical development and adaptation for other imaging targets.

Interested in trying these HP C-13 MR Sequences? Email us at [email protected].


Resource: Sequence Dissemination​
Contact: [email protected]

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HP MRI Tool Box

Reconstruction, Analysis & Visualization Tools (HP MRI Tool Box)

Hyperpolarized MRI Toolbox: The goal of this toolbox is to provide research-level and prototyping software tools for hyperpolarized MRI experiments. It is currently based on MATLAB code, and includes code for designing radiofrequency (RF) pulses, readout gradients, and data reconstruction. 

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Data Analysis Resources

Preclinical Data Analysis Resources 

Videos on Data Visualization and Analysis 

MR Analysis of Hyperpolarized 13C MRI by Dr. Peder Larson: This presentation is from the 2019 HP MRI Course and includes topics such as:
Parametrizations, Ratiometric Methods, Area-under-curve Methods, Simulation Framework for Evaluation of Analysis Methods, 2D Dynamic Analysis, 3D Prostate Cancer Analysis, Kinetic modeling, RD Flip Angle Compensation, Example: Box-car input, two-site kinetic model, Example Fitted input, two-site kinetic model. 
Fitting Methods (Mechanics of model fitting, Robust Fitting, "Input-less" Fitting as a Robust Model, Simulation: Constant flip angles, Simulation: Metabolite-specific flip angles; Metabolite-specific variable flip angles; Fitting bolus characteristics, Fitting T1, Assuming unidirectional conversion, Alternate Tissue Models. Additional Considerations. 
- Hyperpolarized MRI Toolbox, Live Demo

Resource: Course Presentation
Format: PDF or Slides with Audio  (Updated: 08/16/19)
Applicable Research Areas: 
Preclinical & Human Research

Di-chromatic Interpolation of Metabolic Magnetic Resonance Images by Dr. Nicholas Dwork, Postdoctoral ScholarThis presentation is an overview of a publication by Dr. Nicholas Dwork:
Dwork N, Gordon JW, Tang S, O'Connor D, Hansen ESS, Laustsen C, Larson PEZ. Di-chromatic interpolation of magnetic resonance metabolic images. MAGMA. 2021; 34(1):57-72. PMCID: PMC7983744 

Resource: Data Processing Tutorial
Format: Video (.mp4)
(Updated: 05/10/21)
Applicable Research Areas: 
Preclinical & Human Research

 


Human Data Analysis Resources

Videos on Data Visualization and Analysis 

MR Analysis of Hyperpolarized 13C MRI by Dr. Peder Larson: This presentation is from the 2019 HP MRI Course and includes topics such as:
Parametrizations, Ratiometric Methods, Area-under-curve Methods, Simulation Framework for Evaluation of Analysis Methods, 2D Dynamic Analysis, 3D Prostate Cancer Analysis, Kinetic modeling, RD Flip Angle Compensation, Example: Box-car input, two-site kinetic model, Example Fitted input, two-site kinetic model. 
Fitting Methods (Mechanics of model fitting, Robust Fitting, "Input-less" Fitting as a Robust Model, Simulation: Constant flip angles, Simulation: Metabolite-specific flip angles; Metabolite-specific variable flip angles; Fitting bolus characteristics, Fitting T1, Assuming unidirectional conversion, Alternate Tissue Models. Additional Considerations. 
- Hyperpolarized MRI Toolbox, Live Demo

Resource: Course Presentation
Format: PDF or Slides with Audio  (Updated: 08/16/19)
Applicable Research Areas: 
Preclinical & Human Research

Using EPI to investigate HP [1-13C]pyruvate metabolism in glioma patients and healthy volunteers by Dr. Adam Autry: This presentation is from the 2019 HP MRI Course and includes topics such as: Dynamic Echo Planar Imaging (EPI), Dynamic frequency-selective 13C EPI, EPI Processing Framework, Optimal Weights Coil Combination, Voxel-wise Phasing, Regions of Interest, Kinetic traces and fitting: NAWMl, kpl & kpb Maps with ROIs, Serial HP Data.

Resource: Course Presentation
Format: PDF or Audio  
(Updated: August 2019)
Applicable Research Areas: 
Preclinical & Human Research

Image Analysis Techniques 13C MRI in Clinical Study by Dr. Hsin-Yu Chen: This presentation is from the 2019 HP MRI Course and includes topics such as: Challenges in Clinical Mangement of Prostate Cancer, processing HP-13C Prostate Data, Peak Quantification, Phased Detection of Spectra, Phase Correction, Other Quantification Techniques, Receiver Correction, Receiver Correction - Case Study, Transmitter Considerations, Image Display, Masking and ROIs, Quantification of Cancer Metabolism. 

Resource: Course Presentation
Format: PDF or Audio  
(Updated: 09/06/19)
Applicable Research Areas: 
Preclinical & Human Research

Di-chromatic Interpolation of Metabolic Magnetic Resonance Images by Dr. Nicholas Dwork, Postdoctoral ScholarThis presentation is an overview of a publication by Dr. Nicholas Dwork:
Dwork N, Gordon JW, Tang S, O'Connor D, Hansen ESS, Laustsen C, Larson PEZ. Di-chromatic interpolation of magnetic resonance metabolic images. MAGMA. 2021; 34(1):57-72. PMCID: PMC7983744 

Resource: Data Processing Tutorial
Format: Video (.mp4)
(Updated: 05/10/21)
Applicable Research Areas: 
Preclinical & Human Research

Denoising of HP C-13 MR Images of the Human Brain using Patch-based Higher-order Singular Value Decomposition: This presentation is an overview of a publication by Dr. Yaewon Kim: Kim Y, Chen HY, Autry AW, Villanueva-Meyer J, Chang SM, Li Y, Larson PEZ, Brender JR, Krishna MC, Xu D, Vigneron DB, Gordon JW. Denoising of hyperpolarized 13C MR images of the human brain using patch-based higher-order singular value decomposition. Magn Reson Med. 2021 Jun 25. doi: 10.1002/mrm.28887. Epub ahead of print. PMID: 34173268.

Resource: Data Processing Tutorial
Format: Video (.mp4)
(Updated: 07/09/21)
Applicable Research Areas: 
Human Research

Specialized Computational Methods for Denoising, B1 Correction & Kinetic Modeling in HP 13C MR EPSI Studies of Liver Tumors: This presentation is an overview of a publication by Graduate Student Philip Lee from the Vigneron Group: Lee PM, Chen HY, Gordon JW, Zhu Z, Larson PEZ, Dwork N, Van Criekinge M, Carvajal L, Ohliger MA, Wang ZJ, Xu D, Kurhanewicz J, Bok RA, Aggarwal R, Munster PN, Vigneron DB. Specialized computational methods for denoising, B1 correction, and kinetic modeling in hyperpolarized 13C MR EPSI studies of liver tumors. Magn Reson Med. 2021 Jul 3. doi: 10.1002/mrm.28901. Epub ahead of print. PMID: 34216051.

Resource: Data Processing Tutorial
Format: Video (.mp4)
(Updated: 07/09/21)
Applicable Research Areas: 
Human Research

 


Guide for Standardized Methodology Implemented at UCSF for Reproducible Metabolic Imaging Studies of the Prostate and Brain

Citation: Crane JC, Gordon JW, Chen HY, Autry AW, Li Y, Olson MP, Kurhanewicz J, Vigneron DB, Larson PEZ, Xu D. Hyperpolarized 13C MRI data acquisition and analysis in prostate and brain at University of California, San Francisco. NMR Biomed. 2020 Mar 19. doi: 10.1002/nbm.4280. Epub ahead of print. PMCID: PMC7501204. LINK

Purpose & Summary: This is a guide that provides an extensible framework for handling a variety of HP‐13C applications, which derives from two examples with dynamic acquisitions: 3D echo‐planar spectroscopic imaging of the human prostate and frequency‐specific 2D multislice echo‐planar imaging of the human brain. Details of sequence‐specific parameters and processing techniques contained in these examples should enable investigators to effectively tailor studies around individual‐use cases.

ACQUISITION AND DATA FORMATS:  
Acquisition Strategy: 
Current acquisition strategies for HP‐13C MRI can be classified into two categories with specific considerations and trade‐offs in the type of data they produce: (1) spectroscopic imaging methods (chemical shift imaging [CSI]/MR spectroscopic imaging [MRSI]) and (2) imaging‐based methods (eg, echo‐planar imaging [EPI]).
Dynamic Acquisition or Single Time-point:
The other major design choice in the data acquisition is whether to acquire data dynamically or at a single time‐point. We have chosen to acquire dynamic time‐resolved data because it ensures capturing of the bolus in‐flow and is robust to variations in bolus delivery, which can vary between patients due to the injection or physiology. 
2.1 Spectroscopic Imaging Methods: 
The CSI/MRSI‐based strategies acquire data simultaneously from all metabolites and utilize spectrally encoded readouts to resolve the HP substrate from its metabolic products for image synthesis. The echo‐planar spectroscopic imaging (EPSI)‐based acquisition strategies are faster than in conventional phase‐encoded CSI as a result of the multi‐echo readout gradient for spectral encoding. Design of an EPSI readout entails consideration of several key factors. 
2.2 UCSF Prostate Spectroscopic Imaging Strategy: 
Imaging of patients with prostate cancer at UCSF utilizes a 3D compressed sensing (CS)‐EPSI acquisition. Investigations into high‐ versus low‐grade human and preclinical prostate cancer using the 3D CS‐EPSI acquisition were shown to well characterize differences in pyruvate metabolism corresponding to upregulation of lactate dehydrogenase activity. 

 

 

2.3 Imaging-based Methods: 
The metabolite‐specific imaging approach used here is based on a sequence consisting of a single‐band SPSP RF pulse that independently excites each metabolite, followed by a rapid, single‐shot readout to encode the data within a single TR per metabolite/slice. HP 13C MR imaging offers an appealing alternative to EPSI because it can provide higher temporal resolution, is more robust to motion, and can be scaled to large, clinically relevant FOVs without an increase in scan time. 
2.4 UCSF Brain Imaging Strategy: 
HP imaging of patients with brain cancer at UCSF utilizes a frequency‐selective imaging approach with a single‐shot symmetric echo‐planar readout. This approach is well‐suited for the clinical imaging of [1‐13C]pyruvate, where a small number of well‐separated resonances are known a priori.
2.5 RF Excitation Strategies:
The choice of flip angles is crucial in a HP experiment due to the unrecoverable hyperpolarized magnetization, and depends on the temporal resolution and total imaging time. Both spectroscopic imaging and imaging‐based methods (eg, EPI) can benefit from flip angle schemes that vary between metabolites (“multiband” methods) and over time (“variable flip angles”). Multiband methods use a lower flip angle on the substrate compared with the metabolic products, thereby preserving substrate magnetization for future conversion to metabolic products. For the MRSI/CSI‐based methods, we achieve this by using multiband SPSP RF excitation pulses.
2.6 Acquisition Parameters Required for Reconstruction Analysis: 
Reconstruction of MRSI and MRI data requires knowledge of the k‐space and time sampling, typically through characterization of the gradients.
2.7 HP Data Formats: 
At UCSF, the strategy to address these issues has been to (1) standardize the parameterization of acquisitions and to encode this information in a consistent format called the data acquisition descriptor (DAD), and (2) to convert data encoded in vendor‐specific formats to a standard DICOM format to improve interoperability with different software packages and data flows.

 

 

RECONSTRUCTION METHODS:
3.1 EPSI Reconstruction: 
Our 3D CS‐EPSI sequence uses a pseudorandom undersampling encode pattern that travels in (kx,ky) to allow random sampling of data in (kx,ky,kf, dynamic) dimensions. In the case of multichannel data, a singular value decomposition (SVD) algorithm is applied to simultaneously benefit from parallel imaging and CS. 
3.2 EPI Reconstruction: 
Our metabolite‐specific imaging sequence uses a symmetric echo‐planar readout. A symmetric readout is used instead of a flyback readout because of its higher SNR efficiency, reduced echo‐spacing and shorter TE. For multichannel data, prewhitening is also applied to the raw data to account for noise correlation between elements.
3.3 Coil Combination:
Multichannel arrays are used in 13C studies to improve SNR, increase volumetric coverage and enable acceleration. Coil combination code is available in the “hyperpolarized‐mri‐toolbox” (see the supporting information). In the context of this communication, coil combination was performed in multichannel arrays for brain, whereas prostate imaging used a single‐element receiver.

 

DATA POSTPROCESSING AND QUANTIFICATION:
4.1 SNR Thresholding: 
Prior to performing quantifications, we perform thresholding based on the [1‐13C]pyruvate SNR.  
4.2 Noise Considerations: 
Whenever possible we avoid the use of magnitude data, as this can lead to bias at low SNR. In MRSI processing, we use phase‐sensitive peak detection and integration, resulting in real‐valued (ie, can be negative) peak data. 
4.3 Metabolite Extraction: 
Following data reconstruction, we perform several postprocessing steps prior to quantification. Please read the full publication for more details. 
4.4 Quantification of Metabolic Conversion:
We primarily use area‐under‐(time)‐curve ratiometric methods as well as an input‐less kinetic modeling approach for human studies. The rationale for using these methods is that they have been shown to be robust to variations in polarization, SNR and pyruvate delivery, which can be considerable among human subjects. 

VISUALIZATION AND CLINICAL INTEGRATION:
5.1 Visualization: 

At UCSF, we developed a custom software package (SIVIC) to support these requirements. SIVIC reads MRI and MRSI DICOM images as well as multiple vendor‐specific raw data formats.
5.2 Integration with other molecular imaging modalities:  
At UCSF, we have established methods for acquiring and analyzing 1H MRSI for patients with brain tumors. When integrating with HP 13C data, the 1H spectral data and maps can be affinely registered to the 13C data by applying the transformation matrix generated from the registration between the images acquired at two examinations, to enable voxel‐by‐voxel analysis. SIVIC can then be used to provide visual comparisons of 1H and 13C metabolic maps, as well as maps of standardized uptake values64 from PET.

 

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Data and File Sharing

The goals of the HMTRC is to disseminate and provide training in new HP C-13 MRI tools. Please see below for our current offerings on Data and File Sharing: 

  • National Cancer Institute - IND Regulatory & Manufacturing Resources on Hyperpolarized [13C]  Pyruvate 
  • UCSF Box : We use this data sharing platform to support the training, eduction, and tools that are housed on this website. For any questions about documents or specific Box access, please send your request to at [email protected].

Raw & Processed Data Examples, Disease Model Images 

Examples of in vivo animal and human hyperpolarized MRI data can be found by following the links below. These data sets were acquired with different methods and are described more in detail below. 

  • SIVIC Tutorials using Sample in vivo Hyperpolarized datasets: On our SOURCEFORGE page, you can find links to SIVIC tutorials that have been presented at live workshops. The data sets are from specific vendors, but the general concepts should applicable to data from any vendor.
  • Sample in vivo Hyperpolarized MRI Data on GitHubIn the hyperpolarized-mri-toolbox on GitHub, you can access several in vivo hyperpolarized MRI data sets that come from animal and human studies that are acquired with a variety of different methods. Below are some selected examples:

 Rat Kidneys Dynamic MRS Example: This dataset contains slab-selective dynamic MR spectroscopy, acquired in normal rat kidneys.

 Rat Kidneys EPI: This dataset contains pyruvate and lactate dynamic imaging using metabolite-specific imaging with EPI in normal rat kidneys.

 

 TRAMP Mouse Multi-slice EPI: This dataset contains pyruvate and lactate dynamic imaging using metabolite-specific imaging with EPI in a transgenic adenocarcinoma of mouse prostate (TRAMP) mouse model of prostate cancer.

 Human Brain: This dataset contains pyruvate, lactate, and bicarbonate dynamic imaging using metabolite-specific imaging with EPI in the head of a healthy volunteer. 

 

 


 

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