SP #10: Pharmacologic MRI predictors of Treatment Response in Late-Life Depression

Pharmacologic MRI Predictors of Treatment Response in Late-Life Depression


Late-life depression (LLD) affects 15% of Americans over the age of 65. However, conventional treatment for LLD often requires long trials of several antidepressants before an effective regimen can be found for an individual. This process can take many months without any relief from the depressive symptoms. One way of shortening this window of time is to identify which treatment regimen will be the most effective. In a previous study, we used functional MRI to determine the activity associated with LLD treatment response. While high rostral anterior cingulate (rACC) activity predicts good treatment response of mid-life depression, we found that the same was not true for LLD. We also found, however, that a decrease in rACC fMRI activity over time was correlated with better response to antidepressant treatment.   


In this study, we will use pharmacologic functional MRI (phMRI) to characterize the response to serotonin reuptake inhibition (Venlafaxine XR, or VENLA) in LLD. phMRI tracks cerebral blood flow patterns (as proxies of regional brain activity) in response to the initiation and titration of medication. By observing the trajectories of a treatment response, we can use phMRI predictors to identify the earliest point that characterizes a response.


The study design is summarized in Figure 1. Along with repeat fMRI scanning, patients will also undergo detailed cognitive assessment, a clinical interview, and mood and anxiety assessment. Plasma levels of VENLA and its major metabolite (desmethylyenfaxine) will be measured before and after each scan. These measurements of drug levels will be used for correlation with fMRI activation levels.

BTRC Resources Utilized:

TR&D#1: This project requires the use of long data acquisitions on a population that presents imaging challenges due to motion as well as comfort during extended scanning protocols.  While fMRI acquisitions are indeed already short, both our structural and our ASL acquisitions will benefit immediately from the fast and motion-robust rapid imaging techniques being developed in TR&D #1.  Meanwhile, the L+S decomposition was original designed as a robust PCA approach insensitive to outliers, and we will explore the use of L+S methods in fMRI studies.

TR&D#2: We have found that the 7T MR system at the University of Pittsburgh (on which we have previously worked in collaboration with BTRC codirector Dr. Boada) can provide improved spatial resolution for the high resolution scans that we perform in our subjects. Cognitive fMRI at 7T is, however, challenging due to excessive through-plane signal dephasing, which we are currently mitigating through the use of parallel transmission (pTx) methods. We are currently limited to very small flip angles when we use pTx at 7T because of the lack of accurate SAR assessment tools.  Therefore, the SAR characterization tools and the tools for practical parallel transmission being developed in TR&D #2 will be invaluable in helping us increase our flip angles in a safe and reliable fashion. 

Key Personnel: 
Howard Aizenstein, MD, PhD


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Philanthropic Support

We gratefully acknowledge generous support for radiology research at NYU Langone Medical Center from:
• The Big George Foundation
• Raymond and Beverly Sackler
• Bernard and Irene Schwartz

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