histopathological and radiological validation of continuous wave (cw) near infrared spectroscopy...
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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.
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