WEBB FELLOW: Portable Three-dimensional Functional Neuroimaging of Delirium Using Diffuse Optical Tomography

Background:

Delirium is a syndrome of acute brain failure that represents a change from baseline cognitive functioning, characterized by deficits in attention, awareness, and multiple cognitive domains. It is commonly observed in hospitalized patients and is associated with increased mortality, rate of complications, and institutionalization after discharge (McCusker, 2002). Despite its prevalence little is known about its pathophysiology. The advancement of neuroimaging offers the possibility of probing the mechanisms and networks involved in delirium, along with improving our screening, monitoring, and management protocols. Diffuse optical tomography (DOT) is an emerging noninvasive imaging modality that uses near-infrared light to assess changes in brain connectivity (Jiang, 2010). In this study, we used a novel DOT device to capture functional imaging data at bedside in delirious and non-delirious subjects while at rest and while performing a cognitive task.



Methods:

Adults (age 18 and older) of all delirium subtypes were recruited through the consultation-liaison psychiatry service. An admitted, non-delirious cohort (age/gender/hand/admission setting matched) was recruited as well. Three-dimensional, functional imaging was captured in the bilateral dorsolateral prefrontal cortices while at rest and while performing the Months Backwards Test. Data was collected at initial consultation and again after improvement of delirium.


Results:

Preliminary data in five delirious and non-delirious subjects were analyzed. Hemoglobin changes and three-dimensional data were successfully captured while at rest and during task performance. While delirious, subjects were observed to have diminished hemoglobin concentrations, as well as a decreased area of activation. After improvement of delirium, there was noted to be a statistically significant improvement in the peak hemoglobin concentrations, time to peak values, and time of return to baseline. Further comparison with the non-delirious group revealed even more significant differences. 


Discussion:

Previous neuroimaging modalities have been sparse and restricted in their results given their technical limitations (Nitchingham, 2018). No study has simultaneously demonstrated portability, cost-effectiveness, high resolution, and task-based imaging. Our results demonstrate the capability of overcoming such problems. Further statistical and imaging analysis will be conducted to explore the functional connectivity between the prefrontal cortices and other brain regions, along with the correlation between hemoglobin concentrations and assessment tool scores and hospital outcomes.



Conclusion:

In this first-in-human study, we introduced DOT as a novel approach to investigating the mechanisms underlying delirium and its potential to assist with detection, monitoring, and treatment protocols.


References:

1. McCusker J, Cole M, Abrahamowicz M, Primeau F, Belzile E. Delirium predicts 12-month mortality. Arch Intern Med. 2002 Feb 25;162(4):457-63.


2. Jiang, H. Diffuse Optical Tomography: Principles and Applications. CRC Press. 2010.


3. Nitchingham A, Kumar V, Shenkin S, Ferguson KJ, Caplan GA. A systematic review of neuroimaging in delirium: predictors, correlates and consequences. Int J Geriatr Psychiatry. 2018 Nov;33(11):1458-1478.