Aim 1 Enrollment Criteria Inclusion Criteria for Healthy Controls
- Males or females, 10 years to 60 years, with a minimum height for participation of 135 cm
- Ambulatory and able to complete routine clinical exercise testing
- Willing and able to complete all study procedures
- For individuals under the age of 18, parental/guardian permission (informed consent) and as appropriate, child assent
- For individuals over the age of 18 the ability to provide informed consent
Inclusion Criteria for PMD Patients
- Males or females, 10 years to 60 years, with a minimum height for participation of 135 cm
- Ambulatory and able to complete routine clinical exercise testing
- Willing and able to complete all study procedures
- Genetically confirmed mitochondrial myopathy (MM) as defined by a diagnosis of primary mitochondrial disease (PMD) with predominant symptoms of myopathy as expressed by exercise intolerance and muscle weakness and fatigue
- Parental/guardian permission (informed consent) and as appropriate, child assent
Exclusion Criteria for All Aim 1 Participants General Exclusion Criteria
- Tracheostomy
- Non-ambulatory
- Unable to complete routine exercise testing
- Diagnosed with or have symptoms of vertigo
- Within 1 month of a recent hospital admission for acute illness
- Severe co-existing cardiac or pulmonary disease
- Cognitive impairment that may preclude ability to comply with study procedures
- Pregnant or lactating females
- Active alcohol and/or substance abuse
- At the discretion of the principal investigator (PI), any medical condition that will interfere with or prevent the safe completion of the study
- Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures
- Use of investigational agent(s) within 4 weeks
- Individuals who are employed by the U.S. Department of Defense, including U.S military personal
- Patients with biliary atresia with asplenia or polysplenia.
- Patients with prior liver transplant.
- Patients with cystic fibrosis.
- Patients with chronic lung disease.
- Patients with portal vein thrombosis, cavernous transformation of the portal vein or absent portal vein.
- Patients with significant heart disease or severe congenital heart disease.
- Patients with a history of allergic reaction to Lumason®, sulfur hexafluoride, sulfur hexafluoride lipid microsphere components, or other ingredients in Lumason (polyethylene glycol, distearoylphosphatidlycholine (DSPC), dipalmitoylphosphatidylglycerol sodium (DPPG-Na, palmitic acid) or other components of the ultrasound contrast agent
- Any history of intraocular injury or fragment in or around the orbit that cannot be cleared through radiologic evaluation
- Any history of bullet, shrapnel, or stabbing wounds that cannot be cleared through radiologic evaluation
- Past or current employment involving (or exposure to) a metal grinder (e.g., at a construction worksite)
- Claustrophobia or any known medical conditions which can be exacerbated by stress, anxiety, or panic attacks triggered by enclosed spaces
- Inability to lie flat in an MRI scanner for up to 45 minutes
- Unable to perform sub-maximal ankle dorsiflexion leg exercise during the MRI study
Aim 2 Enrollment Criteria Inclusion Criteria for PICU PMD Non-Ambulatory Patients
- Males or females ages 10 to 23 years (children and adults)
- Non-ambulatory
- Genetically confirmed mtDNA-PMD
- Cooperative and capable of following research procedures
- Have cognitive ability to enable cooperation with study procedures
- Admitted to the PICU with an anticipated length of stay for >24 hours
- Willing and able to complete all study procedures
- For individuals under the age of 18, parental/guardian permission (informed consent) and as appropriate, child assent
- For individuals over the age of 18 the ability to provide informed consent
Inclusion Criteria for PICU non-PMD neuromuscular diagnosis
- Males or females ages 10 to 23 years (children and adults)
- Non-ambulatory
- Genetically confirmed non-PMD neuromuscular diagnosis
- Cooperative and capable of following research procedures
- Have cognitive ability to enable cooperation with study procedures
- Admitted to the PICU with an anticipated length of stay for >24 hours
- For individuals under the age of 18, parental/guardian permission (informed consent) and as appropriate, child assent
- For individuals over the age of 18 the ability to provide informed consent
Inclusion Criteria for all other PICU Participants
- Males or females ages 10 to 23 years (children and adults)
- Non-ambulatory
- No known genetic diagnosis with healthy pre-morbid status, admitted to PICU
- Cooperative and capable of following research procedures
- Have cognitive ability to enable cooperation with study procedures
- Admitted to the PICU with an anticipated length of stay for >24 hours
- Willing and able to complete all study procedures
- For individuals under the age of 18, parental/guardian permission (informed consent) and as appropriate, child assent
- For individuals over the age of 18 the ability to provide informed consent
Exclusion Criteria for All Aim 2 Participants
- Have cognitive impairment that may preclude ability to comply with study procedures
- Have cardiorespiratory instability
- Patients in whom are so sick that they will not be able to cooperate with the study procedures
- Have clear contraindications to mobilization
- Have fixed lower limb deformities/contractures that would prohibit lower extremity exercise
- Pregnant or lactating females
- Active alcohol and/or substance abuse
- At the discretion of the principal investigator (PI), any medical condition that will interfere with or prevent the safe completion of the study
- Use of investigational agent(s) within 4 weeks
- Individual who are employed by the U.S. Department of Defense, including U.S military personal
- Patients with biliary atresia with asplenia or polysplenia.
- Patients with prior liver transplant.
- Patients with cystic fibrosis.
- Patients with chronic lung disease.
- Patients with portal vein thrombosis, cavernous transformation of the portal vein or absent portal vein.
- Patients with significant heart disease or severe congenital heart disease.
- Patients with a history of allergic reaction to Lumason®, sulfur hexafluoride, sulfur hexafluoride lipid microsphere components, or other ingredients in Lumason (polyethylene glycol, distearoylphosphatidlycholine (DSPC), dipalmitoylphosphatidylglycerol sodium (DPPG-Na, palmitic acid) or other components of the ultrasound contrast agent
Exclusion Criteria Specific to study procedure: CrCEST MRI Scan:
- Any history of intraocular injury or fragment in or around the orbit that cannot be cleared through radiologic evaluation
- Any history of bullet, shrapnel, or stabbing wounds that cannot be cleared through radiologic evaluation
- Past or current employment involving (or exposure to) a metal grinder (e.g., at a construction worksite)
- Claustrophobia or any known medical conditions which can be exacerbated by stress, anxiety, or panic attacks triggered by enclosed spaces
- Inability to lie flat in an MRI scanner for up to 45 minutes
- Unable to perform sub-maximal ankle dorsiflexion leg exercise during the MRI study