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Intraoperative imaging of the brain macro- and microcirculation
Juan Zhou
Departments of Anesthesia, Pain Management and Perioperative Medicine, Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada

Abstract
Advances in imaging technology have provided new diagnostic methods for assessment of cerebral vascular perfusion and quantitative analysis of the microcirculation£¨Side stream dark field imaging (SDF),Sidestream dark field imaging (SDF)£© during cerebral surgery. In this article, a range of imaging procedures are described: Digital Subtraction Angiography (DSA) and Three-Dimensional Computed Tomography Angiography (3D-CTA), Indocyanine Green Video An¬giography (ICGVA), Orthogonal Polarization Spectral (OPS) Imaging, Sidestream Dark-Field (SDF) Imaging, Sidestream dark field (SDF),and Laser-Doppler Flowmetry (LDF). All these measurements will foster development of precise evaluation tools for microcirculation-re¬lated microvascular conditions, e. g. stroke and hemorrhage, and support clinicians in their thera¬peutic decision-making process.
Key words: angiography, cerebral surgery, intraoperative imaging, microcirculation£¨Side stream dark field imaging (SDF),Sidestream dark field imaging (SDF)£©, macrocirculation
Cerebrovascular surgery is an operative treat-basic principles of brain surgery, but main¬ment for brain vasculature diseases, such as taining the integrity of cerebral microcircula¬aneurysms, arteriovenous malformations, tion is also critical and more challenging for cavernomas, and occlusive vascular diseases function and survival of the tissue cells since like stroke. Traditionally, neurosurgeons di-supply of oxygen and nutrients to individual rectly inspect cerebral vessels with the aid of cells and elimination of waste products from an operating microscope during surgery. To cells occur in the microcirculation£¨Side stream dark field imaging (SDF),Sidestream dark field imaging (SDF),Sidestream dark field (SDF)£© (2). How¬minimize the morbidity and mortality associ-ever, imaging techniques for assessing mi¬ated with the surgical treatment, angiogra-crocirculation in clinical medicine, especial¬phy has been introduced and used as a stan-ly in brain surgery is very limited. In addidard method for preoperative diagnosis and tion, there is a lack of agreement on which postoperative evaluation of the vascular microcirculatory parameters and analyzing anatomy. However, if postoperative angiog-techniques can be used for evaluating the raphy reveals an abnormal surgical result, microcirculation£¨Side stream dark field imaging (SDF),Sidestream dark field imaging (SDF),Sidestream dark field (SDF)£©. This makes the microcircu¬another surgical procedure has to be per-latory study more complex. The aim of this formed for correction or the compromised article is to review techniques of intraopera¬vessel has already caused an infarction. tive imaging at macro- and microcirculation Therefore, intraoperative angiography has in human brain surgery. been applied for evaluating vascular anato¬my and perfusion in real-time (1).
Maintaining the integrity of tissue perfu¬sion through macrovasculature is one of the
Digital Subtraction Angiography (DSA) and Three-Dimensional Computed Tomography Angiography (3D-CTA)
DSA is considered as the ¡°gold standard¡± for detection of cerebral aneurysms and moni¬toring surgical results intraoperatively or postoperatively (3). However, since it¡¯s inva¬sive, time-consuming and technical demand¬ing, intraoperative DSA is not considered as a routine method for all the cases and not available in all the centers. 3D-CTA as anoth¬er diagnostic method in the detection of in¬tracranial aneurysms is found to provide comparable information to DSA, but less in¬vasive, less time consuming, cheaper and easier to demonstrate the essential informa¬tion regarding the aneurysm than DSA (4)(5).
Indocyanine Green Video Angiography (ICGVA)
ICGVA has been used in ophthalmology for many years but applied in brain surgery re¬cently for intraoperative assessment of cere¬bral vasculature in routine or emergency sur¬gery for patients with intracranial aneurysms (6), cerebral arteriovenous or dural fistulous malformations (7), moyamoya disease (8, 9) and decompressive craniectomy for malig¬nant stroke (10). It was performed with a laser-fluorescence imaging device that con¬sisted of a NIR laser light source (0.16 W, =780 nm) and a NIR-sensitive digital cam¬corder. The device was placed 30 to 40 cm from the area of interest and illuminated the area of interest with the laser light source. The NIR laser light emitted from the light source induced fluorescence of ICG, a NIR fluorescent dye injected intravenously. The fluorescence signal was recorded by the dig¬ital video camera with optical filtering to block ambient and laser light for collection of only ICG-induced fluorescence. Angiographic images could be reviewed on the video screen in real time (25 images/s) and stored on the digital video camera or trans¬ferred to a computer (6). ICGVA provides high quality image with spatial resolution that allows assessment of the arterial and venous vessels, including small arteries (<0.5 mm in diameter), and the visible aneurysm sac at real-time. It is a quick, reliable, cost-effective method and clinically useful in aneurysm, dural fistula, and revascularization surgery. It was report¬ed that results obtained from intraoperative ICGVA in all the cases of aneurysms surger¬ies corresponded to the postoperative angiographic finding, but in some cases, the infor¬mation provided by intraoperative ICGVA significantly changed the surgical procedure (6). The major limitation of the method was that the ICG angiographic views were re¬stricted to the angle of the surgical approach. Vessels that were covered by blood clots or aneurysm or brain tissue£¨Side stream dark field imaging (SDF),Sidestream dark field imaging (SDF),Sidestream dark field (SDF)£© could not be ob¬served with this technique (6).
In a recent study, Schnell and co-authors compared advantages and drawbacks of ICGVA and intraoperative computed tomog¬raphy angiography (iCTA) and intraoperative computed perfusion tomography (iCTP) on visualizing brain vasculature during aneurysm surgery (11). They found that ICG-VA was able to detect blood flow and vascu¬lar patency in the vessels only located in the visual field of microscope but not in the deeper areas of surgical field. iCTA provided high quality image in 7/10 patients but could not detect small arteries. iCTP was also able to detect global blood flow in some cases but not in others. Therefore, ICGVA and iCTA/iCTP are complementary rather than competing techniques and able to assess lo¬cal and regional blood flow and cerebral perfusion in intracranial aneurysm surgery (11).
Orthogonal Polarization Spectral (OPS) Imaging
OPS imaging is a noninvasive method for as¬sessing microcirculation(Side stream dark field imaging (SDF),Sidestream dark field imaging (SDF)) on the surfaces of organs. It uses a handheld device with a small optical probe. The tissue is illuminated with linearly polarized light and only depo¬larized photons scattered from the tissue contribute to the imaging (12). It produces high contrast microvascular images that al¬low viewing and quantifying microcirculato¬ry hemodynamic changes at real-time and provides a convenient method for intravital microscopy on the brain surface.
OPS has been used to assess cerebral mi¬crocirculatory changes during brain surgeries of arteriovenous malformation (AVM) (13), aneurysm (14)(15) and tumor removal (16). Parameters of microcirculation£¨Side stream dark field imaging (SDF),Sidestream dark field imaging (SDF),Sidestream dark field (SDF)£©, including di¬ameters of blood vessels, microvascular flow index (MFI), functional capillary index (FCD), flow kinetics and arteriolar contractil¬ity could be evaluated during the surgeries. For example, in AVM surgery, Pennings and coauthors demonstrated that prior to AVM excision, cardiac pulsation was absent in the arterioles and individual erythrocytes were observed due to the slowing of blood flow. However, increased flow velocity (to a level that individual erythrocytes could not be traced), FCD and MFI were observed after re¬section (13). In brain tumor surgeries, stop¬flow and spurt-flow with irregularly shaped vessels and large mean vessel diameters were observed in tumor microcirculation£¨Side stream dark field imaging (SDF),Sidestream dark field imaging (SDF),Sidestream dark field (SDF)£© in comparison to normal healthy cortex, which always expressed continuous flow (16).
Although OPS imaging greatly con¬tributes to study the brain microcirculation, there are still weaknesses by using OPS im¬aging such as motion-induced image blur¬ring caused by movement of the OPS device, the tissue and the blood flowing. In addition, it is difficult to measure flow velocity in large vessels, especially during continuous flow, due to blurring of images (17, 18).
Sidestream Dark-Field (SDF) Imaging
SDF imaging is another noninvasive tech¬nique for continuous observation of cerebral microcirculation on the brain surface during brain surgery. It is a further development of OPS techniques and consists of a handheld videomicroscope containing a ring of strobo¬scopic light emitting diodes (18). Using SDF(Side stream dark field imaging (SDF),Sidestream dark field imaging (SDF)), Perez-Barcena and coauthors reported direct visualization of blood flow and vessel densi¬ty of cerebral microcirculation in patients who underwent decompressive craniectomy after infarction of cerebral artery and the non-stroke control patients who underwent craniotomy for diseases other than stroke (19). The cortical vessels in the control pa¬tients were regularly shaped with continuous blood flow in all sizes of vessels (from 10 to 100 µm in diameters) and the proportion of the perfused vessels was near 100%. The cortical vessels in the patients with stroke showed intermittent or no flow with smaller proportion of perfused vessels (63.44%). The perfused vessels density index was also high¬er in control group than in patients with stroke (19).
However, SDF imaging(Side stream dark field imaging (SDF),Sidestream dark field imaging (SDF),Sidestream dark field (SDF)) cannot directly measure the velocity of erythrocytes since high erythrocyte velocity exceeds the capture rate of the camera for tracing individual red blood cells. In addition, pressure-induced mi¬crocirculatory alterations caused by applica¬tion of the SDF probe onto the tissue surface might lead to false interpretation of actual mi¬crocirculation perfusion (18, 19). In the fu¬ture, new devices with more advanced cam¬era technology may solve the problem for measuring the velocity of erythrocytes.
Laser-Doppler Flowmetry (LDF) and Combined With Photospectrometry
Laser Doppler flowmetry (LDF) was estab¬lished as a noninvasive method for continu¬ous and real-time measurement of blood
flow in the microcirculation£¨Side stream dark field imaging (SDF),Sidestream dark field imaging (SDF),Sidestream dark field (SDF)£©. It measures rel¬ative microcirculatory flow based on the Doppler shift of the illuminated laser light caused by the movement of red blood cells (20). The light is able to penetrate into the depth of tissue and measure microvascular blood flow throughout it, but the depth de¬pends on optical feature, wavelength used and the diameter of the beam (21). LDF has been used in the intraoperative assessment of cortical blood flow during general neuro¬surgical procedures (22) and surgeries for cerebral arteriovenous malformations (23) and various cerebral tumours (24). The major disadvantage is its high sensitivity to motion¬produced disturbances.
Recently, a novel monitoring device (O2C, oxygen-to-see device) based on com¬bined laser-Doppler flowmetry and photo¬spectrometry has been introduced to moni¬tor cortical microcirculation (Side stream dark field imaging (SDF),Sidestream dark field imaging (SDF)) during intracra¬nial surgery (25-27). The device consists of a computer with built-in laser and light emit¬ting diodes and a fiber optic measurement probe. It transmits continuous wave laser light (830nm) and white light (500-800nm) to tissue and collocate the scattered light from tissue to the probe. The Doppler shift of the illuminated laser light is displayed as blood flow velocity while the collected white light is split into its spectral compo¬nents and converted into an electrical signal. Oxygen saturation is determined by compar¬ison with prerecorded deoxygenated and oxygenated hemoglobin spectra, while the tissue hemoglobin values are determined by the amount of light absorbed by the tissue. This device is used only for measurements in the microcirculation (<100 µm diameter) since light from bigger vessels (> 100 µm di¬ameter) is completely absorbed (26, 27). Rel¬ative blood flow is calculated based on the product of moving erythrocytes and velocity of each erythrocyte.
This device£¨Side stream dark field imaging (SDF),Sidestream dark field imaging (SDF),Sidestream dark field (SDF)£© is able to determine regional capillary-venous cerebral blood flow, oxy¬gen saturation and hemoglobin amount si¬multaneously in the cortical/cerebral tissue. It is easy to set up and can be used continu¬ously during brain surgery. Although the depth of measurement is dependent on the distant between the illuminating and detect¬ing elements, the type of probe used and op¬tical characteristics of the tissue, it has been used for measuring cerebral microcirculation from 2 mm to 8 mm of depth. However, this device only provides relative values, not quantitative measurement due to the feature of laser-Doppler flowmetry. In addition, the measurement may be influenced by neuro¬surgery, cortical temperature and blood film in the cerebral cortex (26, 27).
In conclusion, advances in imaging tech¬nology provide new diagnostic methods for assessment of cerebral vasculature perfusion and quantitative analysis of the microcirculation£¨Side stream dark field imaging (SDF),Sidestream dark field imaging (SDF),Sidestream dark field (SDF)£© during cerebral surgery. The measure¬ments will be essential in developing precise tools to evaluate microvascular conditions that may affect the microcirculation, such as stroke or hemorrhage and contribute to the further therapeutic intervention.
References
1 Chiang VL, Gailloud P, Murphy KJ, Riga¬monti D, Tamargo RJ. Routine intraopera¬tive angiography during aneurysm surgery. J Neurosur 2002; 96: 988-92
2 Awan Z a, Wester T, Kvernebo K. Human microvascular imaging: a review of skin and tongue videomicroscopy techniques and analysing variables. Clin Physiol Funct I 2010; 30: 79-88
3 Friedman J a, Kumar R. Intraoperative an¬giography should be standard in cerebral aneurysm surgery. BMC Surgery 2009; 9: 7
4 Chappell ET, Moure FC, Good MC. Com¬parison of Computed Tomographic An¬giography with Digital Subtraction Angiog¬raphy in the Diagnosis of Cerebral Aneurysms: A Meta-analysis. Neurosurgery 2003; 52: 624-31
5 Pechlivanis I, Schmieder K, Scholz M, König M, Heuser L, Harders a. 3-Dimen¬sional computed tomographic angiography for use of surgery planning in patients with intracranial aneurysms. Acta neurochir 2005; 147: 1045-53. ......etc.

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