High-resolution Phosphocreatine and Creatine Mapping of Human Muscle and Brain

In this study, we aim to develop and validate a noninvasive approach for quantifying and imaging energy metabolism, without contrast agents, on widely available clinical MRI scanners. Briefly, this technique allows specific and selective imaging of the energy metabolite phosphocreatine (PCr), in vivo and non-invasively. PCr is one of the predominant high-energy phosphates present in brain and muscle and one that is altered by common diseases. Although energy metabolism and PCr play a vital role in cellular homeostasis, there currently are no routine diagnostic tests to noninvasively quantify or map the distribution of PCr with clinically acceptable spatial resolution or/and scan time. Here, we demonstrate that the exchangeable guanidinium protons of millimolar concentration PCr can be exploited to detect it via the water signal in MRI with greatly enhanced sensitivity (molar signal) using chemical exchange saturation transfer (CEST) MRI, and its concentration can be quantified using an artificial neural network (ANN). This new technique, dubbed ANNCEST, allowed us to obtain a high-resolution PCr map on human skeletal muscle within 1.5 min, on a 3T clinical MRI scanner equipped with just the standard MRI setup. To put this in a larger perspective, energy metabolism is critical for cell viability and is altered by many common acquired and inherited diseases. ANNCEST is arguably the first to use widely available MRI scanners to noninvasively image tissue energy metabolism of PCr, and thus would have appeal to a broad readership of scientists and clinicians interested in neurology, muscular dystrophies and myopathies as well as cardiology, to name a few.

Study Overview

• Status: Recruiting
• Conditions: Healthy

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Jiadi Xu, Ph.D.; Phone Number: 4105980920; Email: xuj@kennedykrieger.org

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205-1832
      • Recruiting
      • F. M. Kirby Center and Johns Hopkins University Medical School
      • Contact: Jiadi Xu; Phone Number: 443-923-9527
      • Principal Investigator: Jiadi Xu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Participants will be recruited from the greater Baltimore area. 50 gender matched healthy controls will be recruited.

Description

Inclusion Criteria:

Subject must be at least 18 years of age Subject must be willing and able to undergo verbal and written informed consent Healthy subjects will have no history of cardiovascular or peripheral vascular disease, diabetes, claudication or difficulty walking.

Exclusion Criteria:

1.) Unable to understand the risks, benefits, and alternatives of participation and give meaningful consent, 2.) Contraindications to MRI such (eg implanted metallic objects) 3.) Significant cardiovascular (heart failure, significant coronary artery disease, infiltrative or hypertrophic cardiomyopathy, constrictive pericarditis), pulmonary or musculoskeletal or orthopedic disease that significantly limit exercise capacity 4.) Weight greater than 350 lbs (inability to fit in the MRI), 5.) Cognitive or speech impairments that would limit completion of questionnaires or fatigue reporting. 6) Subjects with rest pain, critical limb ischemia will be excluded for the study. 7) Pregnant women

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
High-resolution phosphocreatine and creatine mapping of human skeletal muscle and brain	5 years

Collaborators and Investigators

• Sponsor: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
• Collaborators: Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): December 30, 2023
• Study Completion (Estimated): December 30, 2030

Study Registration Dates

• First Submitted: January 16, 2020
• First Submitted That Met QC Criteria: January 16, 2020
• First Posted (Actual): January 21, 2020

Study Record Updates

• Last Update Posted (Actual): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: IRB00072712

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No