Applying pGz in Mitochondrial Disease

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