Clinical trial NCT04234880: High-resolution Phosphocreatine and Creatine Mapping of Human Muscle and Brain
Official title: High-resolution Phosphocreatine and Creatine Mapping of Human Muscle and Brain
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Healthy
Lead sponsor: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Sponsor class: OTHER
Collaborators: name: Johns Hopkins University
First posted: 2020-01-21
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Participants will be recruited from the greater Baltimore area. 50 gender matched healthy controls will be recruited.

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.


Eligibility criteria: 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

Primary outcomes:
measure: High-resolution phosphocreatine and creatine mapping of human skeletal muscle and brain
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: F. M. Kirby Center and Johns Hopkins University Medical School
state: Maryland
Study officials:
References: