NNICU Research Activities

There is a rich tradition of fellow-driven research in the Neurology and Neurosurgery Intensive Care Unit (NNICU) at Washington University. The overall goal of NNICU research is to improve the lives of our patients by enhancing our understanding of acute brain injury pathogenesis. We believe that next-generation treatments will grow best from a solid foundation of disease phenomenology. To this end, we are actively engaged in research spanning the spectrum from true wet-lab studies in animal or cellular models, to multi-center randomized control trials, with every step in between. A particular focus and strength of our research approach is the use of advanced physiological tools, such as PET, advanced MRI, and neuromonitoring technologies, which provide unparalleled information about in vivo human brain function. Lab-based studies are further leveraged to provide mechanistic insights and to frame hypotheses that are then tested with targeted experiments in the ICU. We benefit from several unique resources that permit novel experimental design in the ICU, including a PET scanner in the unit (affectionately known as bed 21), a mini-wet lab in the ICU, and an advanced research imaging center (the CCIR) directly adjacent to the ICU. The CCIR is equipped with multiple research-grade scanners: a 1.5T MRI, a 3T MRI, a separate PET-3T MRI that is prioritized for ICU studies of acute brain injury, and a PET-CT. These scanners are exclusively utilized for research studies. A further strength of Washington University is its exceptionally robust spirit of collaboration. Experts in innumerable techniques and fields are available to support creative research ideas.

In addition to acute physiological research, we maintain a detailed clinical database spanning many years and employ a full-time ICU RN research coordinator as well as a full-time database manager to assist with fellow-driven prospective and retrospective clinical research.

Fellows are expected to complete an academic project during their training. For those seeking more comprehensive training in neurocritical care research, we also offer a research fellowship (see below). All fellows are supported to the fullest extent possible with mentoring, resources, and as much flexibility as clinical training allows. Dr. Michael Diringer leads this effort in his role as chief research mentor. Fellows meet with Dr. Diringer and additional staff mentors regularly throughout their training to receive research guidance. Our fellows have successfully applied for grants during fellowship, presented at international conferences, and published their research in peer-reviewed journals. We look forward to discussing your ideas!


Research fellowship

A 3-year research and clinical fellowship is available for exceptionally-motivated trainees seeking a career as a research neurointensivist. This fellowship is unique in combining rigorous clinical training with strategic blocks of independent research time and intensive mentorship. Graduates of this fellowship will have a successful track record of publication and grant funding, and be equipped to start a career with a developed scientific skill set and focus. For more information, contact Dr. Rajat Dhar.


Faculty Research Interests

Dhar_R Rajat Dhar, MD
Cerebral edema, imaging, genetics, and PET physiology
My bibliography link (pubmed)
Kummer_T Terrance Kummer, MD, PhD
Acute vascular and traumatic brain injury, animal models, diffusion MRI approaches, cerebral metabolism, bench-to-bedside translation
My bibliography link
https://hopecenter.wustl.edu/?faculty=terrence-kummer-md-phd
Phuah Chia-Ling Phuah, MD, PhD
Stroke genetics
My bibliography link
Diringer_M Michael Diringer, MD
Subarachnoid hemorrhage, intracerebral hemorrhage, PET physiology
My bibliography link
Allen_M Michelle Allen, RN
NNICU Research Coordinator

Clinical Trials

Minimally Invasive Surgery plus rt-PA in the treatment of Intracerebral Hemorrhage (MISTIE III)
A phase III, randomized, open-label, 500-subject clinical trial of minimally invasive surgery plus rt-PA in the treatment of intracerebral hemorrhage.
PI: Michael Diringer

SANGUINATE
A phase IIa, single escalating-dose, open-label study to assess the safety and effect of SANGUINATE™ Infusion in patients at risk of Delayed Cerebral Ischemia after acute aneurysmal subarachnoid hemorrhage, assessed with PET.
PI: Rajat Dhar

Factor Xa Variant
A phase 1B multicenter, open-label study to evaluate the safety and tolerability and determine the maximum tolerated dose of PF-05230907, a reversal agent for direct thrombin inhibitors, in subjects with intracerebral hemorrhage.
PI: Michael Diringer

SAGE-547
A randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of SAGE-547 injection in the treatment of subjects with super-refractory status epilepticus.
PI: Edward Hogan

ACTION-2
A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Parallel-Group Does-Ranging Study to Evaluate the Safety and Efficacy of Intravenous Natalizumab (BG00002) in Acute Ischemic Stroke
PI: Jin-Moo Lee

RHAPSODY
A Multicenter, Phase 2 Study Using a Continual Reassessment Method to Determine the Safety and Tolerability of 3K3A-APC, a Recombinant Variant of Human Activated Protein C (APC), in Combination with Tissue Plasminogen Activator (tPA) in Moderately Severe Acute Hemispheric Ischemic Stroke
PI: Jin-Moo Lee

NAME TBD
A Phase 2, Placebo Controlled, Randomized, Double-Blind, Parallel-Arm Study to Evaluate
Efficacy and Safety of BMS-986141 For the Prevention of Recurrent Brain Infarction in Subjects receiving acetylsalicylic acid (ASA) following Acute Ischemic Stroke or Transient Ischemic Attack
PI: Andria Ford

Immunomodulation in Severe Sepsis
Phase 1b/2a, randomized, double-blinded, placebo-controlled, multicenter study to evaluate the safety, tolerability, pharmacokinetics & pharmacodynamics of an immunomodulatory agent, BMS-936559, in subjects with severe sepsis.
PI: Richard Hotchkiss


Images

Diffusion tensor imaging MRI of mouse brain after subarachnoid hemorrhage demonstrating reduced diffusion anisotropy in white matter structures after injury. Electron microscopic evidence of axonal injury in background. From Kummer et al, 2015.

Advanced diffusion MRI techniques (A) demonstrate unique tissue contrast (arrowheads) in mouse models of brain injury. Loss of dendritic spines following TBI (B-C).

Advanced diffusion MRI techniques (A) demonstrate unique tissue contrast (arrowheads) in mouse models of brain injury. Loss of dendritic spines following TBI (B-C).

PET with co-registered CT showing hyper-perfusion in an area of evolving edema after subarachnoid hemorrhage

PET with co-registered CT showing hyper-perfusion in an area of evolving edema after subarachnoid hemorrhage

Research coordinator Michelle Allen facilitating a research PET scan on our in-ICU PET scanner (“bed 21”).

Research coordinator Michelle Allen facilitating a research PET scan on our in-ICU PET scanner (“bed 21”).

Example of CT-based volumetric edema analysis after a hemispheric stroke

Example of CT-based volumetric edema analysis after a hemispheric stroke