Atherosclerosis in cocaine addiction: imaging risk with PET/MR

Cocaine use disorder (CUD) can cause vascular disease mainly through chronic vasoconstriction effects.
Atherosclerosis can be present in the carotid artery (CA) even without overt clinical symptoms. Once symptoms are
observable, the artery is usually damaged and cerebral ischemia can ensue, a common fatal outcome in CUD.
Indeed, while there are postmortem studies documenting arterial disease in individuals with CUD (iCUD), studies for
early in-vivo detection lag behind with catastrophic consequences. Here we will leverage the significant advances
made in imaging for early detection of atherosclerosis in asymptomatic populations who are nevertheless at
increased risk for vascular disease by MPI Fayad; such early detection is crucial for guiding prevention efforts.
Specifically, we will use a hybrid scanner whereby positron emission tomography (PET) with the radiotracer 18F-
fluorodeoxyglucose (18F-FDG) quantifies vessel-wall inflammation in atherosclerotic plaques while magnetic
resonance imaging (MRI) with a 3-dimensional (3D) dark-blood scan characterizes carotid plaque burden. Such
simultaneous state-of-the-art previously validated PET/MRI CA imaging has never before been applied for early
atherosclerosis detection in asymptomatic drug addicted individuals. Targeting this population for early detection is
of particular urgency now that the “Crack generation” (of the mid 80s) is aging. Following decades of cocaine and
comorbid tobacco and alcohol use, these iCUD are at an especially high risk for vascular disease and
atherosclerosis. Nevertheless, given factors inherent to drug addiction, relevant diagnoses in this population are only
made when it is too late to intervene (hence the preponderance of post-mortem studies). We hypothesize that
markers of CA atherosclerosis will be detected in asymptomatic iCUD, as related to their cocaine, tobacco, and
alcohol use, at levels comparable, or even surpassing, those detected in individuals with known risk factors for
cardiovascular disease but without CUD. The bilateral internal CAs are the primary conduits of oxygenated blood to
the cerebral hemispheres and indeed individuals with cardiovascular disease demonstrate cognitive decline
(especially of attention, memory and executive function), recently suggested to be modulated by brain network
connectivity (especially in brain networks innervated by the internal CAs and subserving salience/control and reward
processing) as measured by resting-state functional MRI. Following a series of studies conducted by MPIs Alia-Klein
and Goldstein, where similar resting-state inefficiencies were reported in iCUD, modulated by severity of drug use
and accompanied by similar cognitive dysfunction, here we postulate that the CA disease markers in iCUD will
correlate with neural network connectivity and cognitive function. Beyond the mechanistic inventiveness of this
proposal, linking of the carotid to brain function for the first time in drug addiction, it also addresses a public health
imperative for early detection of the preclinical markers of atherosclerosis in iCUD. Once pathology is identified, and
especially if identified at an early stage, timely intervention can prevent the progression into emergencies,
impairments and premature mortality that comprise an enormous cost to society.

Grant Number: 5R01DA049547-05
NIH Institute/Center: NIH
Principal Investigator: Nelly Alia-Klein