Assessing the Prognosis of Pulmonary Embolism Using Clinical and Imaging Biomarkers (Retrospective & Prospective )

Venous thromboembolism (VTE), which clinically manifests as deep vein thrombosis (DVT) and
pulmonary embolism (PE), is a common but elusive illness that can cause significant
disability and death if not promptly diagnosed and effectively treated. The annual incidence
of VTE in the United States is estimated at 1 per 1000. Death occurs in approximately 12% of
PE cases within 1 month of diagnosis. At present, clinical management of VTE and PE is
hampered by gaps in our understanding of pathogenic mechanisms, the wide variety in patient
populations, and incomplete understanding of the long term risks of recurrence and death.
Given the complex presentation and risk associated with these conditions, proper risk
assessment and subsequent prophylaxis for all at-risk patients is crucial. While clinical
prediction rules have been recently developed to associate short-term risks and to stratify
patients with acute PE, there is a dearth of objective biomarkers that can be related to the
long-term prognosis of the disease. In addition to clinical information, clot burden is
known to be strongly associated with clinical outcome of recurrent VTE. The quantification
of clot burden requires imaging.

CT Pulmonary Angiography (CTPA) has been established as a reference imaging standard in the
diagnosis of PE. In addition to its role as a superb diagnostic tool, CTPA contains a wealth
of information including characteristics of the clot that may be used as biomarkers
associated with prognosis of PE. The work proposed in this application takes advantage of
widely available CTPA imaging biomarker data and extends and advances clinical PE risk
prediction model to include long term (2-year) survival as well as the clinically important
outcome of recurrence. The primary objective of this proposal is to develop and identify
CTPA imaging biomarkers that are associated with short-term and long-term prognoses of
patients who were positively diagnosed for PE by CT. The rationale for this proposal is that
CT imaging is a rich source of imaging biomarkers that may be associated with prognosis of
PE. This information will help advance our understanding of the risk and recurrence of PE
and provide a new insight to prognosis and clinical management and treatment of PE. This
proposed research is innovative in that we have developed new CT imaging biomarkers and
designed a clinical trial to assess and validate the prognostic values of these biomarkers.
Our central hypothesis is that CT imaging biomarkers are associated with the risk of death
and recurrence in patients with PE. The specific aims of this proposal are: (1) to quantify
and characterize pulmonary emboli (volume and distribution) and comorbid
cardiovasculopulmonary findings from CT images of patients who were positively diagnosed for
PE by CT; (2) to identify CT imaging biomarkers that are associated with the prognosis of
patients who were positively diagnosed for PE by CT, and to develop risk prediction tools
for death and recurrence; and (3) to prospectively validate the risk prediction tool, and
identify whether the change in CT imaging biomarkers of PE after initiation of therapy
improve the predictive ability for recurrence and death.