• At screening, female participants must be nonpregnant and nonlactating.
• In good physical health on the basis of no clinically significant findings from medical history, PEs, laboratory tests, ECGs, and vital signs.
• Participant is a carrier of a loss of function GRN mutation or carrier of a hexanucleotide repeat expansion C9orf72 mutation.

• Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins. 
• History of alcohol abuse or substance abuse.
• Participant resides in a skilled nursing facility, convalescent home, or long term care facility.

• Aged 18 years and older.
• Normal subjects must not have any confounding medical conditions.

Exclusion Criteria:

• Any ‘undefined’ metallic implants or foreign bodies inside the body.
• Implanted active devices such as cardiac defibrillators/pacemakers, deep brain stimulators, vagus nerve stimulators, intrathecal pumps, cochlear implants.
• Devices, or residual parts thereof left in the body such as cardiac pacer wires, which provide life assist, bone growth or pain management.
• Structural support devices, screws, or wires in bone that are near the spinal cord or temperature sensitive organs.
• Reconstructive metallic implants near the orbits.
• External devices, medicinal patches, piercings, jewelry, clothing or hair accessories (such as wigs, weaves and extensions) within to the radiofrequency coil that cannot be removed from the body.
• Pregnancy.
• Prisoners.
• Tattoos located within or near the radiofrequency coil.
• Permanent facial makeup (for brain scanning).
• Metallic fragment in the eye.
• Colored contact lens.
• Fever / elevated temperature.
• Suffer from claustrophobia.

• Patients ≥ 18 years old.
• Patients undergoing plasma exchange therapy for a medical indication.

• Age < 18 years old.

• Patients older than 18 years old.
• Males or females.
• Patients who came in for cardioversion for atrial fibrillation.

• Poor image quality.

Inclusion Criteria - For Roll-over Patients from Trial HS-18-633:

• Patients who attend the Week 24 visit of the preceding trial (HS-18-633) and are willing to continue their participation in this trial.
• Written informed consent of the patient.
• Patients must be willing to use an acceptable method of contraception during the entire trial.

Inclusion Criteria - For New Patients:

• Able to provide written informed consent to participate in the trial prior to any
  trial-related procedures are performed .
• Willingness and ability to comply with the requirements of the protocol.
• Male or female patients, ≥ 18 years at screening.
• Diagnosis of acromegaly by historical evidence of (persistent or recurrent) acromegaly
  as documented by:
  • IGF-1 levels > 1 x ULN;
  • Pituitary adenoma on magnetic resonance imaging (MRI) or pathology report Computerized tomography (CT) is accepted if MRI could not be performed;
  • IGF-1 levels >1 x ULN measured at least 3 months after the surgery for patients who have undergone pituitary surgery.
• Treatment with a stable dose of octreotide LAR (10 mg, 20 mg, 30 mg or 40 mg) or
  lanreotide ATG (60 mg, 90 mg or 120 mg) for at least 3 months as monotherapy prior to
  screening.
• IGF-1 levels >1 x ULN and ≤ 2.0 x ULN at screening (adjusted for age and sex; mean
  value of the first measurement at screening and the second measurement at 2 weeks
  before Day 1) with or without prior pituitary radiotherapy (at least 3 years prior to
  screening), or IGF-1 levels ≤ 1 x ULN at screening (adjusted for age and sex; mean value of the first measurement at screening and the second measurement at 2 weeks before Day 1), with prior pituitary radiotherapy at least 3 years prior to screening and confirmed disease activity defined as IGF-1 levels > 1 x ULN during drug holiday 3 to 9 months prior to
  screening.
• Patients must have adequate liver, pancreatic, renal and bone marrow functions:
  • Adequate liver function:
    • Total serum bilirubin ≤ 1.5 x ULN*;
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2 x ULN;
    • International normalized ratio (INR) < 1.3.
  • Adequate pancreatic function:
    • Amylase and lipase ≤ 2 x ULN.
  • Adequate renal function:
    • Estimated glomerular filtration rate ≥ 60 mL/min by the Modification of Diet in Renal Disease formula.
  • Adequate bone marrow function:
    • Platelets ≥ 100 x 10^9/L;
    • Hemoglobin > 9 g/dL;
    • White blood cells > 3.0 x 10^9L.

*Patients with previous diagnose of Gilbert’s syndrome may be included if the disease is not
accompanied by other hepatobiliary disorders and if the total bilirubin is < 3 mg/dL
(< 51.3 μmol/L) and the direct bilirubin is ≤ ULN.

• Normal ECG defined as the following as determined by the mean value of a triplicate ECG:
  • Resting heart rate 50-105 bpm;
  • QTc interval corrected by Fridericia’s formula (QTcF) <450 msec.
• Female patients of childbearing potential must be willing to use an acceptable method of contraception during the entire trial.
• Male patients must be willing to use condoms throughout the trial unless they have been sterilized by vasectomy (with an appropriate post-vasectomy documentation of the absence of sperm in the ejaculate).

For Roll-over Patients from Trial HS-18-633

• Unresolved, drug-related serious adverse event (SAE) from the preceding trial (HS-18-633).
• Patients who, based on the Investigator's judgment, have a clinically significant or unstable medical or surgical condition that may preclude safe and complete trial participation. Conditions may include cardiovascular, peripheral vascular, pulmonary, hepatic, renal, or neurological disease, as determined by physical examination, laboratory tests or ECG.
• Pregnancy.

For New Patients

• Have received medical treatment for acromegaly with pasireotide (within 6 months prior to screening), pegvisomant (within 3 months prior to screening), dopamine agonists (within 3 months prior to screening) or other investigational agents (within 30 days or 5 half-lives prior to screening [whichever is longer]).
• Currently receiving other treatments known to affect GH or IGF-1 concentration (including oral estrogens for e.g. contraception or replacement treatment in hypogonadism or during menopause).
• Patients who usually take octreotide LAR or lanreotide ATG less frequently than every 4 weeks (e.g. every 6 weeks or 8 weeks).
• Compression of the optic chiasm causing any visual field defect for whom surgical intervention is indicated.
• Patients who have undergone major surgery/surgical therapy for any cause within 1 month from screening. Patients who have undergone surgery more than 1 month from screening must have recovered from the treatment and be in good clinical condition.
• Patients who have undergone pituitary surgery within 6 months prior to screening
• Patients who have received prior pituitary irradiation within 3 years prior to screening
• A history of another primary malignancy except the following:
  • Stable and well-differentiated microcarcinoma of the thyroid
  • Non-melanoma skin cancer, and carcinoma in situ of the cervix, uterus, or breast from which the patient has been disease-free for ≥3 years
  • A primary malignancy that has been completely resected and in complete remission for ≥5 years.
• Participation in any other clinical trial to test an investigational drug or device within the last 30 days before screening
• Patients with poorly controlled diabetes mellitus, defined as hemoglobin A1c (HbA1c) >8.0%
• Patients with diabetes mellitus who have initiated treatment with insulin or who have changed the insulin treatment regimen within 6 weeks prior to screening
• Hepatic/pancreatic-related exclusion criteria
  • Presence of hepatitis B surface antigen
  • Current hepatitis C virus infection
  • History of alcohol/drug misuse within the past 12 months
  • Patients with symptomatic cholelithiasis within 3 months from screening (patients with non-symptomatic cholelithiasis/sludge and patients who have undergone cholecystectomy more than 1 month from screening can be included in the trial)
• Patients with presence of active or suspected acute or chronic uncontrolled infection or
• immunocompromised patients, including patients with positive human
• immunodeficiency virus (HIV) test result
• Cardiac exclusion criteria: cardiac or cardiac repolarization abnormality, including any
• of the following:
  • a. History of myocardial infarction, angina pectoris or coronary artery bypass graft
  • within 6 months prior to screening
  • b. Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete
  • left bundle branch block, high-grade atrioventricular (AV) block (e.g. bifascicular
  • block, Mobitz type II and third-degree AV block)
  • c. Long QT syndrome, family history of idiopathic sudden death or congenital long
  • QT syndrome, or any of the following:
  • i. Risk factors for Torsades de Pointes including uncorrected hypokalemia or
  • hypomagnesemia, history of cardiac failure or history of clinically
  • significant/symptomatic bradycardia
  • ii. Concomitant medication(s) with a “Known risk of Torsades de Pointes” that cannot be discontinued or replaced by
  • safe alternative medication/s. A wash-out of 5 half-lives or 7 days
  • (whichever is longer) from previous treatment with drugs with a known
  • risk of Torsades de Pointes is required prior to the first dose of CAM2029
  • iii. Inability to determine the QTcF interval
• Uncontrolled hypertension defined by a systolic blood pressure >160 mmHg and/or
• diastolic blood pressure >100 mmHg. The patient needs to be on a stable dose of
• antihypertensive medication for at least 4 weeks before screening
• Untreated or uncontrolled hypothyroidism, hypoadrenalism or diabetes insipidus.
• Patients must be adequately treated with stable doses of replacement therapy for a
• minimum of 3 months prior to screening
• Any other current or prior medical condition that may interfere with the conduct of the
• trial or the evaluation of its results in the opinion of the Investigator or the Sponsor’s
• Medical Monitor
• Pregnant, lactating or planning to be pregnant during the trial
• Clinically significant laboratory abnormalities, which in the opinion of the Investigator
• may prevent the patients from safely participating in the trial
• Any known allergy, hypersensitivity or intolerance to octreotide or any related drug, or
• history of any drug hypersensitivity or intolerance which in the opinion of the
• Investigator, would compromise the safety of the patient or the trial
• Any other contraindicated serious medical condition, which in the opinion of the
• Investigator may prevent the patients from safely participating in the trial.
• Unwilling or unable to comply with the requirements of the protocol or in a situation or  condition that, in the opinion of the Investigator, may interfere with participation in the trial.
• On the staff, affiliated with, or a family member of the personnel directly involved with this trial.

• Age 18 or older.
• Scleral lens wearers with a history of 6 months of at least 5 hours of scleral lens wear at least 5 days/week are invited to participate.

• Patients with active infections or unstable inflammation of the eyes are not eligible to participate.
• Patients who have been refit into a different scleral lens design during the past 6 months.
• Patients who are actively participating in the scleral lens fitting process.

• Patients 18 years and older.
• Patients who are undergoing elective defibrillation threshold testing of their transvenous ICD or defibrillation threshold testing of the subcutaneous ICD at the time of implantation.

• Patients under age 18 years old.
• Patients with myocardial infarction, coronary artery bypass grafting or any invasive cardiac procedure in the previous six weeks.
• Pregnant patients.
• Patients who cannot provide informed consent because of cognitive dysfunction.

• Age 18-80 years.
• Recipient of kidney transplantation 4 or more years.
• Competent and able to provide written informed consent.
• Ability to comply with protocol.

• Patients have clinically significant medical conditions within the prior 6 months before: e.g. myocardial infarction, congestive heart failure, or stroke, that would, in the opinion of the investigators, compromise the safety of the patient.
• Severe chronic liver, heart, or lung disease.
• Undergoing acute rejection.
• Contra-indication to biopsy; bleeding disorders.
• Chronic infection.
• Any active malignancy and undergoing therapy.
• Kidney or ureteric stone.
• Unable to give valid informed consent.
• Known pregnancy or intent to conceive during the study period.
• Pacemaker, implantable defibrillator, magnetically active metal fragments, claustrophobia, or other contraindication to MRI.
• Federal medical center inmates.

Eligibility last updated 9/13/22. Questions regarding updates should be directed to the study team contact.

• Patients with epilepsy having previously undergone brain imaging using a 7T MRI scanner as part of their diagnostic evaluation.

• Patients in which a prior 3T brain MRI was diagnostic for an epileptogenic lesion at the time of initial interpretation.
• Prospective patients who do not sign and return the HIPAA use consent form.
• Patients with large, confounding cerebral pathologies such as large infarcts or brain tumors.
• Patients with poor 7T image quality due head motion or other technical issues

• Individuals between 18 and 65 years of age.
• Individuals who have undergone surgical reconstruction of the brachial plexus.
• Individuals in good neuromuscular health with no previous musculoskeletal disease

• Individuals under 18 or over 65 years of age

• Adult patients 18 years or older. 
• Patients with Glasgow coma scale score (GCS) ≤ 8
• Patients having neuroimaging concerning for ICP crises or have active ICP treatment may undergo non-invasive NIRS monitoring and invasive LICOX intraparenchymal brain tissue oxygen monitoring once study consent is obtained.

• Patients with CNS infection.
• Patients with bleeding diathesis or thrombocytopenia < 50,000 platelets.
• Patients with subdural hematomas who have had surgical decompression and bone flap removal.
• Each patient will undergo 3 to 10 days of monitoring (depending on pathology; i.e., patients with poor-grade aneurysmal subarachnoid hemorrhage may undergo longer monitoring to assess for delayed cerebral ischemia during the time window of vasospasm risk).
• Pregnant individuals.
• Children.
• Prisoners.
• Institutionalized individuals.
• Others who are likely to be vulnerable.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 7/28/22. Questions regarding updates should be directed to the study team contact

• Bone marrow hypocellular for age.
• Moderate or severe aplastic anemia defined by one of the following: peripheral blood neutrophils < 0.5 x 10^9/L; platelets < 30 x 10^9/L or platelet transfusion dependence; reticulocytes < 50 x 10^9/L in anemic patients or red cell transfusion dependence.
• Diagnosis of dyskeratosis congenita based on clinical triad of abnormalities of skin pigmentation, nail dystrophy, oral leukoplakia; OR one of clinical triad and presence of two or more associated features; OR a pathogenic mutation in DKC1,TERC, TERT, NOP10, NHP2, TCAB1, TINF2, CTC1, PARN, RTEL1, or ACD as reported by a CLIA-approved laboratory; OR age-adjusted mean telomere length < 1%ile in peripheral blood lymphocytes as reported by a CLIA-approved laboratory; OR Hoyeraal-Hreidarsson syndrome; OR Revesz syndrome
• Availability of a related or unrelated donor with a 7/8 or 8/8 match for HLA-A, B, C, and DRB1.
• Patient and/or legal guardian must be able to sign informed consent.
• Donor must provide a marrow allograft.
• Diagnosis of Fanconi anemia must be excluded by mitomycin C or diepoxybutane chromosomal breakage testing on peripheral blood at a CLIA-approved laboratory (not required for patients with a genetic mutation consistent with DC).
• Adequate renal function with glomerular filtration rate equal to or greater than 30 ml/min/1.73 m2.

• Clonal cytogenetic abnormalities associated with MDS or AML on bone marrow examination.
• Karnofsky/Lansky performance status < 40.
• Uncontrolled bacterial, viral or fungal infections.
• Positive test for the human immunodeficiency virus (HIV).
• Pregnancy or breastfeeding.
• Known severe or life-threatening allergy or intolerance to fludarabine, alemtuzumab, cyclosporine, or mycophenolate mofetil.
• Positive patient anti-donor HLA antibody, which is deemed clinically significant.
• Prior allogeneic marrow or stem cell transplantation.
• Prior solid organ transplantation.

• Adult patients (age >= 18 years old).
• Suspected WHO grade II or III infiltrating glioma based on standard MR imaging.
• No previous tumor treatment or surgery.
• Surgery for definitive diagnosis anticipated to occur within 3 months of study imaging.

• Inability to undergo MR imaging for any reason (claustrophobia, habitus, implanted devices, etc.).
• Previous cranial surgical operations if metallic plates or grafts are near the area of tumor.
• Predominantly ring-enhancing disease on anatomic MR.
• Pregnancy.

• Patients age ≥ 18 years old.
• Either scheduled to receive or have received a kidney transplant (KT) at Mayo Clinic Rochester, Mayo Clinic Arizona, or Mayo Clinic Florida.

• Neuropsychiatric condition causing patient to be unable to provide consent.
• Scheduled to receive a combined organ transplant.

• Healthy, non-obese participants.
• Non-pregnant Caucasian volunteers.
• 18-70 years old.
• Male or female, 1:1.
• BMI < 30kg/m2.

• Diabetes.
• Hypertension.
• BMI ≥ 30kg/m^2.
• Chronic NSAID use (> 3 days/week).

• Patients age ≥ 18 years.
• Have received a kidney transplantation.
• Have a functioning allograft.

• Neuropsychiatric condition causing patient to be unable to provide consent.
• Recipient of a combined organ transplant.

• Self-identifies as Somali.
• Between 18 and 75 years of age.
• Receives primary care at Mayo Clinic ECH.
• Visited the primary care site at least once in the least twelve months.
• Intention to continue receiving care at the clinic for the next six months.
• Diagnosis of T2D in medical record.
• T2D diagnosis for six months or longer.
• Most recent hemoglobin A1c ≥ 8%.

• Not eligible if someone in the same household is participating in the study.

• Age ≥ 18 years old.
• New myocardial infarction within 10 days of enrollment

• Contraindications to MRI scanning including internal defibrillators or pacemakers, cerebral aneurysm clips, or severe claustrophobia.  
• Contraindications to gadolinium-based MRI contrast material; namely, glomerular filtration rate less than or equal to 30mL/min. 
• Patients with no serum creatinine available within 30 days will have a new serum creatinine drawn to calculate glomerular filtration rate. 
• Women who are pregnant or lactating.

• Patients 18-70 years old.
• Patients having ischemic stroke in the past 5 years.
• Diagnosis of ischemic stroke when between 18 and 64 years of age.

• Patients under 18 or over 70 years of age.

• Subject shall have a unilateral amputated lower limb for no less than 12 months. If the amputation needed revision within 12 months, patient could be enrolled if investigator documents that the amputation site has healed and subject’s symptoms have stabilized.
• Post-amputation pain shall be chronic (persistent over 6 months) and resistant to pain medications with a documented history within the subject’s medical records.
• Subject shall have frequent and recurring pain defined as no less than 4 episodes of pain ≥ 5 (NRS) per week on average (to be confirmed with baseline pain diary).
• Subject’s typical pain episode should last no less than 60 minutes.
• Subject shall demonstrate response to two injections, one regional nerve block and the other saline. Response to the regional nerve block is defined as greater than or equal to a 50% pain reduction by NRS at 20 minutes from administration of Lidocaine. An allowable, non-therapeutic response to saline is defined as less than 30% pain reduction by NRS 15 minutes after administration. NRS must be ≥ 5 before first injection.
• Subject’s regimen of drug therapy for pain shall be stable for no less than 4 weeks prior to implant and shall not change without approval of investigator until after their Month- 3 visit. Subject shall sign a pain medication “contract” to confirm acceptance of guidelines for the use of pain medication.
• Subject agrees not to replace or alter their prosthetic (if applicable) until after their Month-3 (primary endpoint) visit.
• Subject is able to independently read and complete all questionnaires provided in English and use electronic diary during study.
• Subject is willing and able to provide informed consent and comply with all procedures and assessments required by study protocol.
• Subject, and caregiver if applicable, is able and willing to be available for study visits throughout the duration of the study; e.g., no planned relocation of residence or extended vacation during the study that would prevent compliance with study visit schedule.
• Subject shall be 21 years of age or older (FDA definition of non-pediatric) and legally able to provide written informed consent.

• Implanted with an active implantable medical device (i.e., pacemaker).
• Confounding source of pain that interferes with reporting of limb pain.
• Uncontrolled diabetes.
• Spasticity preventing full range of motion of involved side .
• Extremely short stump; sits on end.
• Untreated psychological condition (i.e., borderline personality).
• Condition requiring MRI studies or diathermy after device implant.
• Life expectancy of less than 24 months.
• Progressive neurological disease (i.e, multiple sclerosis).
• Subjects with active local or systemic infection or immunocompromised.

• Subject is currently implanted with any active implantable device including but not limited to: pacemaker, implantable cardiac defibrillator, implantable neurostimulator (e.g., peripheral or spinal cord stimulator), or implantable drug pump.
• Subject has a source of pain other than post-amputation pain (incl. dysesthesia, cancer- related, visceral, angina, migraine, causalgia) which in the opinion of the investigator may interfere with the reporting of post-amputation pain.
• Subject has medical contraindications to surgery, including but not limited to cardiovascular, pulmonary, renal, liver or hematological disorders, active inflammation, medical contraindication for general anesthesia (e.g., severe cardiopulmonary disease), compromised immune state (due to concomitant disease or medications such as chemotherapy or immunosuppressants), or anticoagulant medication that cannot be discontinued for perioperative period.
• Uncontrolled diabetes as defined by HbA1c > 8.0.
• Spasticity in their residual limb such that the subject cannot achieve volitional full range of motion (ROM) of joints on involved side.
• Subject has skin graft or severe scarring over targeted implant site or any anatomical conditions that would prevent placement of the Altius System components.
• Subject demonstrates an inability to discern differences in pain severity, report pain intensity and related information, or complete a pain diary.
• Subject has a suspected or known allergy to any materials of the Altius System in tissue contact or Lidocaine (necessary for injection screen).
• Subject has received therapeutic regional nerve block (e.g., anesthetic with steroid, and/or opioids) for post-amputation pain within 30 days prior to baseline visit.
• Subject’s usual seated posture includes sitting on the end of their stump.
• Subject is a woman who is not using adequate contraception, is pregnant or breastfeeding, or intends to become pregnant during the course of the study.
• Subject is currently participating or intends to participate in another investigational drug or device clinical study that may influence or interfere with the data that will be collected for this study.
• Subject has a condition requiring MRI studies or diathermy after device implantation.
• Subject has a history of any alcohol or substance abuse or dependence which has required prior medical treatment or intervention. Subject has active alcohol or substance abuse.
• Subject has a condition that, in the opinion of the investigator, would interfere with study compliance (incl. unresolved issues of secondary gain) or subject’s safety.
• Subject has a life expectancy of less than 24 months.
• Subject is diagnosed with or has untreated psychological conditions: borderline personality disorder, major depression disorder characterized by hospitalization within the prior year for a major depressive episode.
• Subject has current diagnosis of any progressive neurological disease such as multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, rapidly progressive diabetic peripheral neuropathy, or any tumor of the nervous system.
• Subjects with active local or systemic infection, prior recurrent bacterial infection, those who are immunocompromised or have high risk of infection due to other comorbidities.

• Adult male and non-pregnant women 18 years old or older.
• Subject has suspected temporal arteritis.
• Subject is scheduled for TAB based on clinical diagnostic protocol.
• Subject is able to understand the study procedure and provide informed consent.

• Subject has an established prior diagnosis of temporal arteritis/giant cell arteritis.
• Subject is pregnant or breast feeding.
• Subject is unable to provide informed consent.

• Aged 18 or older who are the primary caregivers of patients listed (active, deferred, or temporarily inactive) for lung, heart/lung, or heart transplantation at Mayo Clinic in Rochester, MN and Jacksonville, FL.

• Individuals younger than 18.
• Those who are non-English speaking, non-verbal, or extremely hard of hearing.

• Age 18 and older.
• Aneurysmal subarachnoid hemorrhage (SAH) in anterior/middle posterior circulation  cerebral compartment.
• Aneurysm must be secured endovascular with coiling.
• The patient or patient’s surrogate should be able to give informed consent and understand the risks of this study.
• Pain NRS ≥ 5/10 in severity.

• Non aneurysmal, traumatic subarachnoid hemorrhage (SAH).
• Transcranial Doppler velocities suggestive of or approaching vasospasm.
• Pregnancy.

• Patients with Barrett's Esophagus (BE) undergoing endoscopic surveillance.

• Patients with contraindications to endoscopic resection and/or volumetric laser endomicroscopy (VLE) imaging.

• Individuals between the ages of 18-30 years old.
• No current cervical spine pain or condition that would compromise the ability to perform a maximal isometric contraction of the cervical musculature. 
• No pain with screening evaluation consisting of active flexion, extension, side bending and negative Spurling’s compression test.
• No disability based on NDI scores (less than 4 points out of 50 possible points).

• Current neck pain or diagnoses cervical pathology.
• Past history of cervical spine surgery or pain with cervical screening.

• Subjects from 18 to 99 years of age.
• Aims 1 and 4
  •subjects from daily schedules of those scanners for the brain or MSK studies.
• Aims 2 and 3 - collaboration with the Departments of Neurology, Neurosurgery, and Physical Medicine and Rehabilitation for recruitment of subjects that may be identified by clinical colleagues or via the log of patients that are potential candidates to receive an implanted MR conditional device and passed on to the study team for screening. 

• The subject has an MR unsafe implanted device. Similarly subjects who have foreign metallic objects which contraindicate having an MRI exam (e.g., shrapnel).
• If all the labeled conditions cannot be met at the location of the device for a particular subject (e.g., due to the location of their device, no x-ray available, or other some other reason), that subject will not be scanned on the Compact 3T as part of this protocol. As described above in Methods (step 5), this may result in a screen failure.
• Pregnant or nursing subjects.

• Patient has a Class I or IIa indication for implantation of an ICD according to the ACC/AHA/HRS Guidelines, or ESC guidelines. 
• Patient is at least 18 years of age and meets age requirements per local law. 
• Patient is geographically stable and willing and able to complete the study procedures and visits for the duration of the follow-up.

• Patient is unwilling or unable to personally provide Informed Consent. 
• Patient has indications for bradycardia pacing or Cardiac Resynchronization Therapy (CRT) (Class I, IIa, or IIb indication). 
• Patient with an existing pacemaker, ICD, or CRT device implant or leads. 
• Patients with these medical interventions are excluded from participation in the study: 
  • Prior sternotomy;
  • Any prior medical condition or procedure that leads to adhesions in the anterior mediastinal space (i.e., prior mediastinal instrumentation, mediastinitis);
  • Prior abdominal surgery in the epigastric region;
  • Planned sternotomy;
  • Prior chest radiotherapy Or any other prior/planned medical intervention not listed that precludes their participation in the opinion of the Investigator.
• Patient has previous pericarditis that:
  • Was chronic and recurrent; or
  • Resulted in pericardial effusion; or
  • Resulted in pericardial thickening or calcification. 
• Patients with these medical conditions or anatomies are excluded from participation in the study: 
  • Hiatal hernia that distorts mediastinal anatomy;
  • Marked sternal abnormality (e.g., pectus excavatum);
  • Decompensated heart failure;
  • COPD with oxygen dependence;
  • Gross hepatosplenomegaly.
• Or any other known medical condition or anatomy type not listed that precludes their participation in the opinion of the Investigator.
• Patients with a medical condition that precludes them from undergoing defibrillation testing: 
  • Severe aortic stenosis;
  • Intracardiac LA or LV thrombus;
  • Severe proximal three-vessel or left main coronary artery disease without revascularization;
  • Hemodynamic instability;
  • Unstable angina;
  • Recent stroke or transient ischemic attack (within the last 6 months);
  • Known inadequate external defibrillation; 
  • LVEF < 20%;
  • LVEDD > 70 mm.
• Or any other known medical condition not listed that precludes their participation in the opinion of the Investigator. 
• Patient with any evidence of active infection or undergoing treatment for an infection. 
• Patient is contraindicated from temporary suspension of oral/systemic anticoagulation.
• Patient with current implantation of neurostimulator or any other chronically implanted device that delivers current in the body. 
• Patient meets ACC/AHA/HRS or ESC clinical guideline Class III criteria for an ICD (e.g., life expectancy of less than 12 months). 
• Patient is enrolled or planning to enroll in a concurrent clinical study that may confound the results of this study, without documented pre-approval from a Medtronic study manager. 
• Patient with any exclusion criteria as required by local law (e.g., age or other).
• Pregnant women or breastfeeding women, or women of child bearing potential and who are not on a reliable form of birth regulation method or abstinence.

​​​​​​

• Ability to understand and willingness to provide informed consent.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, aged ≥ 18 years.
• Diagnosed with Stage IV metastatic melanoma, or inoperable Stage III equivalent.
• FDG-PET/CT scan available to serve as baseline; the archived scan date must be within 30 days prior to date of enrollment (date initial ICF signed); images from external facilities are allowed. If no archived FDG-PET/CT scan in window, the baseline scan must be obtained at Screening.
• Complete blood count with differential, within 14 calendar days prior to enrollment, demonstrating the following:
  • White blood cells (WBC) > 2500/mm^3;
  • Hemoglobin (Hgb) > 9.0 g/dL;
  • Platelets > 60,000/mm^3;
  • Absolute Neutrophil Count (ANC) > 1,250/mm^3
    • If no differential is available in the SOC results for enrollment, a subject may be enrolled without the ANC level. Following enrollment, however, this criterion must be met to proceed in the study.
• Comprehensive metabolic panel, within 14 calendar days prior to enrollment, demonstrating values within the site’s upper limit of normal (ULN), with the following exceptions:
  • Alanine aminotransferase (ALT) ≤ 3 x ULN;
  • Aspartate aminotransferase (AST) ≤ 3 x ULN;
  • Alkaline phosphatase (ALP) ≤ 2.5 x ULN.
• Ability to lie flat and still for a minimum of two hours for the SPECT scan.
• For females of reproductive potential: use of highly effective contraception for at least one month prior to screening, and agreement to use such a method during study participation and for an additional four weeks after the end of last investigational imaging agent administration.
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner during study participation and for an additional four weeks after the end of last investigational imaging agent administration.
• Agreement to adhere to Lifestyle Considerations throughout study duration.
• Documented life expectancy of at least 3 months.
• Access to most recent biopsy is requested (if tissue is available) at screen or if it is obtained through SOC during an expanded window of acceptability; i.e., throughout entire conduct of study at this site. (An updated consent will be obtained.) If a biopsy is completed as part of routine clinical care prior to IRB closure, the study may request access to this sample for tissue MC1R staining and analysis.

• Active secondary malignancy.
• Prior treatment (for any reason) with radioactive nuclides; imaging tracers are acceptable.
• Pregnancy.
• Lactation.
• Febrile illness within 48 hours of scheduled imaging procedure.
• Uncontrolled infection.
• Treatment with another investigational drug within 30 days prior to enrollment date.
• Subjects initiating BRAFi drugs between baseline FDG scan and enrollment. Subjects receiving consistent, stable therapy with BRAFi for ≥ 3 months prior to enrollment and who have persistent FDG positive malignant lesions on PET imaging are eligible.
• eGFR < 50 mL/min/1.73m^2.
• BMI > 50 kg/m^2.
• Previous medical history of a condition resulting in anaphylaxis or angioedema.
• Planned treatment while on study with concomitant investigative agents that do not have disclosed safety profiles in the melanoma population (peer-reviewed publications and investigator’s brochures for phase 2 or 3 trials will be accepted as disclosed safety profiles).

Eligibility last updated 11/10/21. Questions regarding updates should be directed to the study team contact.

• Patients positive for rheumatoid factor and/or anti-CCP antibodies.
• Patients with CAD documented by prior bypass surgery, prior placing of coronary stents of prior documentation of myocardial infarction
• Healthy Controls:
  • > 60 years of age;
  • No history of cardiovascular disease based on evaluation of a physician.

• Chronic viral infection.
• History of chemo/radiotherapy.
• History of cancer.
•  
• Healthy Controls:
  • Hx of autoimmune disease;
  • Hx of chemo/radiotherapy.
• History of cancer (with the exception of basal cell carcinoma of the skin).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 1/18/23. Questions regarding updates should be directed to the study team contact.