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

NCT04234880 | Recruiting

• 1 other identifier: IRB00072712
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• High-resolution phosphocreatine and creatine mapping of human skeletal muscle and brain

  5 years

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

• 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.

You may not qualify if:

• ) 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

Sponsors & Collaborators

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

Study Sites (1)

F. M. Kirby Center and Johns Hopkins University Medical School

Baltimore, Maryland, 21205-1832, United States

RECRUITING

Central Study Contacts

Jiadi Xu, Ph.D.

CONTACT

4105980920; xuj@kennedykrieger.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 16, 2020
• First Posted: January 21, 2020
• Study Start: January 1, 2018
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2030
• Last Updated: March 7, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)