Histopathological and Radiological Histopathological and Radiological Validation of Continuous Wave (CW) Near Validation of Continuous Wave (CW) Near Infrared Spectroscopy (NIRS) Recordings Infrared Spectroscopy (NIRS) Recordings

During Cerebral Intravascular ManipulationsDuring Cerebral Intravascular Manipulations

Daniel C. Lee, M.D.

Cardiothoracic SurgeryState University of New York

Downstate Medical Center

Introduction

• Prevalent neurological complications associated with surgery

• Neurocognitive impairment in 50% of patients after coronary bypass procedure - declined quality of life

• 600,000 open heart procedures/year at $100,000 hospital cost per case

• Neuroprotection pertinent in improving quality of life and medical economics

Introduction• Currently available intraoperative cerebral monitoring

inadequate

– Intracranial pressure, regional cerebral blood flow, jugular venous oxygen saturation monitoring – invasive

– Sensitivity of transcranial Doppler limited by bony cranium

– EEG requires trained neurologist, does not measure tissue oxygenation

– Low-density NIRS oximetry neglects heterogeneity of cerebral perfusion

Introduction• Clinical need of intraoperative cerebral

monitoring tool– Real-time

– Temporal and spatial specificity

– Identify ischemia/hypoperfusion at a reversible stage to allow countermeasures

• ? NIRS tomography

• Controlled cerebral ischemia studies needed for validation

Study Aim

Validate capability of NIRS tomography in cerebral monitoring using a non-human primate (NHP: Bonnet Macaque) model of acute cerebral ischemia

Methods

NIRS Imager:

• Continuous-wave (CW), f-NIRS 3D Diffuse Optical Tomography (3D-DOT)

• Two wavelengths (760 and 830 nm)

• Time-series imaging: 8 Hz image framing rate • 270-channel array (30 detector optodes, 9 coupled with light

sources)

Methods• Stroke model 2-3 hour unilateral microcatheter

occlusion of the middle cerebral artery (MCA) of anesthetized NHP

• Continuous recordings of Hbtotal, Hboxy, Hbdeoxy concentration from each channel of the array– 4×5 cm2 area in the frontal-parietal region of the exposed monkey

skull

– 3D image reconstruction• Post-procedure MRI and post-mortem histopathology of

brain performed

Monitored Events of Interest

• Intra-arterial Verapamil (vasodilator) injection

• Intra-arterial contrast (OmnipaqueTM) injection– Mimicking transient ischemia

• Localized acute cerebral ischemia

• Subarachnoid hemorrhage (SAH)

Lateral Digital Subtraction Angiogram Before Microcatheter Occlusion

• Normal cerebral vascular anatomy and the circle of Willis (red circle). before right MCA occlusion

• CCA–common carotid artery• ECA – external carotid artery • ICA –internal carotid artery• MCA – middle cerebral artery• ACA – anterior cerebral artery

• Elements of the fNIRS optode array mounted to the animal’s cranium also are visible.

Right MCA

Azygous ACA

Left MCA

Right ICA

Right CCARight ECA

fNIRS array

Optical fibers

Anteroposterior Digital Substraction Angiogram

Image confirmation of occlusion of the right MCA

Intra-arterial ICA catheter occluding right MCA

fNIRS optode array

Lateral Fluoroscopy

Right Hemisphere NIRS monitoring Optodes directly over confirmed stroke site

Begin Occlusion

End Occlusion

Left Hemisphere NIRS monitoring: optodes positioned over contralateral side

Begin occlusion

End occlusion

Lateral Digital Subtraction Angiogram Demonstrating Subarachnoid Hemorrhage:

Internal Carotid Artery Perforation

Insertion of catheter in the right ICA

Catheter moved from right ICA to the left ICA

Contrast injection

Beginning of subarachnoid hemorrhage

Begin Left ICA/MCA occlusion

End Left ICA/MCA occlusion

Left Hemisphere NIRS monitoring: optodes positioned over site of acute cerebral ischemia

Verapamil injections

Contrast injections

Start of subarachnoid hemorrhage

Begin Left ICA/MCA occlusion

Insertion of catheter into the right ICA

Catheter moved from the right ICA to the left CA

End of left ICA/MCA occlusion

Right Hemisphere NIRS monitoring optodes positioned over contralateral side

Right MCA Verapamil injection 3D DOT image reconstruction

Before After

Axial

section

Right

Sagittal

section

Right MCA Contrast injection3D DOT image reconstruction

Before After Animation

Axial

section

Right

Sagittal

section

Acute Cerebral Ischemia of the right (NHP-1) and left (NHP-2) hemispheres

Before [NHP-1] After Before [NHP-2] After

Axial

section

Coronal

section

Diffuse Bilateral Subarachnoid Hemorrhage (SAH)

Before [NHP-1] After Before [NHP-2] After

Axial

section

Coronal

section

Diffuse Bilateral Subarachnoid Hemorrhage (SAH)

Before After Animation

Axial

section

Coronal FLAIR MRI sequences (NHP-2)

R LLR

Confirmation of: 1) ischemia (dotted circle) in the left temporal and inferior frontal lobe; 2) the presence of SAH (arrow points).

Gross pathology and histologic findings for NHP-1.

• A) SAH present in the sulci.

• B) Hemorrhage in subarachnoid space (>) and vasculature ( ).

• C, D) Vacuolization of neuropil () and shrunken neurons with hypereosinophilic cytoplasm (◄) indicate acute ischemic damage.

Gross pathology and histologic findings for NHP-2.

• A) Subarachnoid hemorrhage over the brainstem and Circle of Willis.

• B) Subarachnoid hemorrhage in the sulci.

• C) Photomicrograph of the hemorrhage in the subarachnoid space ( >)

Conclusions•NIRS Tomography accurately captured cerebral ischemia, vasodilatation, and hemorrhage in an experimental primate model in real time, with spatial and temporal specificity

•Utilization for cerebral monitoring in a clinical setting (intraoperative, trauma/critical care) may be promising

Acknowledgments• Surgery

– Tigran Gevorgyan, John Kral• Pathology

– Douglas Pfeil, Harry Graber, Yong Xu, Jenny Libien, Randall Barbour

• Interventional Neuroradiology– Sundeep Mangla

• Neurology– Frank Barone

• Anesthesia– Jean Charchaflieh

• This research was supported by the National Institutes of Health under Grants nos. R21NS067278, R42NS050007 and R44NS049734; by the Defense Advanced Research Projects Agency (DARPA) project N66001-10-C-2008; and by New York State Department of Health ECRIP Grants to Randall Barbour and Daniel Lee.