Evaluation of Pulmonary Perfusion Heterogeneity and Compliance in Patients With Pulmonary Hypertension Using Positron Emission Tomography Imaging

Pulmonary hypertension (PH) refers to abnormalities in the pulmonary vasculature associated
with a diverse group of disorders. The World Health Organization (WHO) classifies pulmonary
hypertension into five groups, with Group I comprising pulmonary arterial hypertension
(formerly referred to as "primary pulmonary hypertension"). Although not currently a part of
the WHO classification, exercise-induced pulmonary arterial hypertension (EIPAH), defined by
normal pulmonary artery pressures at rest and elevation of pulmonary pressures with exercise,
is increasingly recognized as a distinct clinical entity. In some patients, exercise-induced
pulmonary hypertension may represent a precursor for developing an established elevation in
pulmonary pressures at rest that defines PAH. Functional PET imaging has not previously been
utilized to quantify perfusion and vascular compliance in patients with pulmonary arterial
hypertension. The overall goal of this study is to evaluate regional lung perfusion,
perfusion heterogeneity, and vascular compliance in patients with both exercise-induced and
resting pulmonary hypertension using functional positron emission tomography imaging.
Ultimately, if quantifiable differences between healthy subjects and patients with PAH are
detected with 13NN and 11CO labeled PET, functional PET imaging may provide a useful imaging
modality in early diagnosis of pulmonary hypertension and monitoring response to therapy. In
this pilot study, we will recruit 10 adult patients with pulmonary hypertension (5 with PAH
and 5 with EIPAH) who are on stable PAH-specific therapy (if any), and 5 healthy controls.

Inclusion Criteria:

- General

1. A signed and dated written informed consent is obtained from the subject.

2. The subject is capable of giving informed consent, which includes compliance with
the requirements and restrictions listed in the consent form.

3. Available to complete the study.

4. Able to lie flat and able to perform a 30 second breath hold.

- Patients with Pulmonary Hypertension

1. Subject is male or female aged = or > 18 years of age and < or = 70 years.

2. Subject is diagnosed with pulmonary arterial hypertension (WHO Group I, by right
heart catheterization, mean PA pressure > 25 and PCWP < 15) or exercise-induced
pulmonary hypertension (by right heart catheterization + Level III
cardiopulmonary exercise testing, mean PAP > 30 and PCWP < 20 during exercise,
but normal at rest), with the most recent of above diagnostic tests taking place
within 12 months of study entry.

3. If patient has been on PAH-specific therapy, the therapy (agent and dose) has
been unchanged for at least 3 months.

Exclusion Criteria:

- General

1. FEV1 and/or TLC < 70% predicted

2. PCWP > 15 mm Hg

3. Inability to perform the study (by primary MD or investigator assessment)

4. Subjects who have a past or present disease, which as judged by the Investigators
may affect the outcome of this study

5. The subject has suspected history of drugs or alcohol abuse within the six months
prior to the screening visit.

6. The subject has a positive pregnancy test.

7. The subject is unable to perform the respiratory manoeuvres necessary for the
exam.

8. The subject has been exposed to a radiation dose over the past year that, when
added to the radiation dose expected in this study, would exceed permissible
yearly exposure as determined by the MGH radiation safety committee.

- Subjects with Pulmonary Hypertension

1. Subject with clinical instability in the judgment of the investigator, or
hospitalization for progression of pulmonary hypertension or right heart failure
in the three months prior to the study.

2. Subjects in whom PAH therapy has been escalated (additional agent started) within
3 months of enrolment.

3. Subject with diagnosis of active tuberculosis, lung cancer, clinically overt
bronchiectasis, allergic rhinitis, asthma, or COPD.

4. Subject that had a respiratory tract infection in the 4 weeks prior to the
screening visit and throughout the duration of the study.