J Neurosurg 50:560-569, 1979
`
`Superficial temporal artery to middle cerebral
`artery anastomosis
`
`Intraoperative ~valuation by fluorescein angiography
`and xenon-133 clearance
`
`JOHN R. LITTLE, M.D., F.R.C.S.(C.), Y. LUCAS YAMAMOTO, M.D., PH.D.,
`WILLIAM FEINDEL, M.D., F.R.C.S.(C.), ERNST MEYER, M.Sc., AND
`CHARLES P. HODGE, R.B.P.
`
`Department of Neurology and Neurosurgery and the Cone Laboratory for Neurosurgical Research,
`Montreal Neurological Institute and McGill University, Montreal, Quebec, Canada
`
`J;I Fluorescein angiography and xenon-133 {133Xe) clearance studies were performed during surgery on 15
`patients who were undergoing superficial temporal artery (STA) to middle cerebral artery (MCA)
`anastomosis. Fourteen patients h~d occlusive disease of the internal carotid artery (ICA), and one patient
`had severe stenosis of the MCA. Before anastomosis, fluorescein angiography showed slow filling of the
`MCA branches through collateral channels. Focal areas of impaired microcirculatory filling and washout
`were seen in the territory of severely sclerotic cortical arteries. The findings of preanastomotic 13SX:e
`clearance studies were variable and a uniform pattern of regional cerebral blood flow (rCBF) changes was
`not defined. In 55% of the patients, rCBF was reduced to 25 ml/100 gm/min or less at one or more detector
`sites. Fluorescein angiography provided an immediate assessment of anastomotic patency and clearly dis(cid:173)
`played the distribution of blood entering the epicerebral circulation through the ST A. In 67% of patients,
`multiple MCA cortical branches filled with fluorescein, whereas in 33% filling was restricted to the receptor
`artery territory. An immediate, substantial(~ 15 mlf 100 gm/min) increase in rCBF was demonstrated in
`73% of patients after anastomosis. The rCBF changes were consistently better in patients with donor and
`receptor arteries greater than 1 mm in diameter. Redistribution of collateral input acted to increase rCBF in
`areas distant from the anastomotic site. Some improvement in fluorescein circulation and rCBF also was
`seen in cortex supplied by sclerotic MCA branches.
`
`KEY WORDS
`• cerebral ischemia
`fluorescein angiography
`
`• cerebral revascularization
`
`• cerebral blood flow
`
`·
`
`CEREBRAL blood flow (CBF) in patients undergo(cid:173)
`
`ing superficial temporal artery (ST A) to mid(cid:173)
`dle cerebral artery (MCA) anastomosis has
`been studied before and after surgery by Schmiedek,
`et al., 18 Yamamoto, et al., 12•23•24 and others. 1• 14 These
`investigations demonstrated reduced regional cerebral
`blood flow (rCBF), usually multifocal, in the cerebral
`hemisphere ipsilateral to the occluded internal carotid
`artery (ICA) or MCA. The revascularization
`procedure consistently improved rCBF, and symp(cid:173)
`toms of cerebral ischemia invariably did not recur.
`
`Information about the changes in the epicerebral
`circulation and rCBF during surgery is limited. Ex(cid:173)
`perimental studies have been performed on dogs, 15•16
`but the results, although interesting, are difficult to
`relate to the human situation. The object of this in(cid:173)
`vestigation was to study the epicerebral circulation
`and rCBF during surgery in patients undergoing ST A(cid:173)
`MCA anastomosis for occlusive disease of the ICA or
`MCA. This was accomplished using fluorescein
`angiography and the xenon-133 (133Xe) clearance
`technique.
`
`560
`
`J. Neurosurg. / Volume 50 / May, 1979
`
`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`Novadaq Technologies Inc. Exhibit 2001 Page 1
`
`

`

`Intraoperative evaluation of STA-MCA anastomosis
`
`TABLE 1
`Clinical presentation and diagnostic findings in 15 patients undergoing ST A-MCA anastomosis*
`
`Clinical
`Localization
`of Cerebral
`lschemia
`
`Angiographic
`Findings
`
`CT Scan
`Findings
`
`Case
`No.
`
`1
`
`2
`
`Sex,
`Age
`(yrs)
`
`M,
`44
`M,
`59
`
`Clinical
`Diagnosis
`
`recent small stroke,
`TIA'S
`recent small stroke,
`TIA's
`
`recent small stroke
`
`recent small stroke,
`It amaurosis fugax
`recent small stroke,
`TIA'S
`recent small stroke
`
`recent small stroke,
`TIA's
`old It cerebral stroke,
`TIA's
`recent small stroke,
`TIA's
`recent small stroke
`
`. recent small stroke,
`TIA'S
`recent small stroke,
`TIA's
`TIA's
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`M,
`68
`M,
`60
`M,
`50
`M,
`63
`F,
`60
`M,
`51
`F,
`61
`M,
`16
`M,
`55
`F,
`47
`M,
`53
`F,
`old It cerebral stroke,
`TIA's
`47
`M,
`recent small stroke
`39
`TIA's
`*STA = superficial temporal artery; MCA = middle cerebral artery; TIA = transient ischemic attacks; ICA = internal carotid
`artery; ECA = external carotid artery; CCA = common carotid artery; CT = computerized tomography .
`
`h
`I
`1:
`
`·I
`:1
`:I
`,I
`"'
`
`rt fronto-
`parietal
`It frontal,
`It parieto-
`occipital
`It frontal
`
`It parietal
`
`rt frontal
`
`It parietal,
`rt frontal
`It frontal
`
`rt fronto-
`parietal
`rt fronto-
`parietal
`rt frontal
`
`rt frontal
`
`It fronto-
`parietal
`lt frontal
`
`It fronto-
`parietal
`lt frontal
`
`rt ICA stenosis
`(diffuse)
`It ICA occlusion,
`lt ECA stenosis (95 %),
`rt CCA occlusion
`It ICA occlusion
`
`lt ICA occlusion,
`It ECA $tenosis (50%)
`rt ICA occlusion
`
`lt & rt ICA occlusion,
`It ECA stenosis (95 %)
`lt ICA stenosis
`(supraclinoid)
`rt & lt ICA occlusion,
`rt ECA stenosis (70 %)
`rt ICA occlusion,
`rt ECA stenosis (95 %)
`rt ICA stenosis
`(supraclinoid)
`rt ICA occlusion
`
`no abnormality
`
`no abnormality
`
`small It cerebral
`infarction
`small It cerebral
`infarction
`small rt cerebral
`infarction
`bilateral cerebral
`infarction
`no abnormality
`
`large It cerebral
`infarction (old)
`small rt cerebral
`infarction
`small rt cerebral
`infarction
`no abnormality
`
`It ICA occlusion,
`It ECA stenosis (90 %)
`It ICA occlusion
`
`no abnormality
`
`no abno~ity
`
`lt ICA occlusion
`
`lt MCA stenosis
`
`lt cerebral
`infarction
`no abnormality
`
`• ,
`
`r
`
`Clinical Material and Methods
`
`Patient Population
`
`133Xe clearance
`Fluorescein angiography and
`studies were performed during surgery on 15 patients
`(Table 1) undergoing STA to MCA anastomosis. The
`11 men and 4 women ranged in age from 16 to 68
`years (mean: 51 years). Atherosclerosis was the
`primary pathological process in the 14 adults. The
`arteriopathy in the 16-year-old male patient (Case 10)
`was thought to be the result of homocystinuria.
`
`Clinical Presentation
`Eleven patients presented with cerebral transient
`ischemic attacks (TIA's) in the MCA distribution.
`Nine of them had also suffered a recent ( < 3 months
`ago) small cerebral infarct. One patient (Case 4) had
`recurrent amaurosis fugax and had suffered a recent
`
`small, ipsilateral infarct. The three remaining patients
`had experienced recent cerebral infarction only.
`
`Cerebral Angiography
`Preoperative angiography with visualization of the
`aortic arch, vertebral arteries, and carotid arteries
`(both intracranially and extracranially) was carried
`out in each case. lpsilateral occlusion of the ICA was
`demonstrated in 11 patients. Inaccessible ICA
`stenosis was seen in three patients, including the 16-
`year-old boy (Case 10) who was shown to have
`progressive, severe stenosis of the supraclinoid seg(cid:173)
`ment. Four patients with ICA occlusive disease also
`had focal, high-grade (~ 90%) stenosis at the origin of
`the ipsilateral external carotid artery (ECA). They un(cid:173)
`derwent external carotid endarterectomy with inser(cid:173)
`tion of a vein-patch graft 2 weeks before craniotomy.
`Another patient (Case 8) with a 70% focal stenosis of
`the proximal ECA had an external carotid endarterec-
`
`J. Neurosurg. / Volume 50 / May, 1979
`
`561
`
`Novadaq Technologies Inc. Exhibit 2001 Page 2
`
`

`

`J. R. Little, Y. L. Yamamoto, W. Feindel, E. Meyer and C. P. Hodge
`
`tomy performed 2 weeks after craniotomy. Severe,
`focal stenosis of the MCA trunk was demonstrated in
`Case 15.
`
`Operative Procedure
`A No. 18 polyethylene catheter was inserted per(cid:173)
`cutaneously into the ipsilateral common carotid artery
`(CCA) immediately before surgery. The catheter was
`intermittently irrigated with small amounts of
`heparinized saline ( 1000 units/ 500 ml isotonic saline)
`throughout the operation to prevent thrombus forma(cid:173)
`tion and to maintain catheter patency.
`An inverted U-shaped scalp flap was turned. The
`larger ST A branch, together with a generous cuff of
`connective
`tissue, was mobilized carefully. A
`relatively large temporoparietal craniotomy was per(cid:173)
`formed. The largest exposed cortical artery, usually
`the angular branch of the MCA, was selected as the
`receptor vessel. Mean STA diameter was 1.3 mm
`(range: 0.9 to 1.6 mm) and mean receptor artery
`diameter was 1.2 mm (range: 0.9 to 1.6- mm). Con(cid:173)
`tinuous suturing 11 was performed for the anastomosis
`in all but the initial three patients, in whom the stan(cid:173)
`dard interrupted suture technique was used. The
`operations were carried out by one surgeon (J.R.L.).
`The arterial blood pressure was mainta.ined at
`preoperative levels during the intraoperative studies.
`Arterial pC02 ~.as kept in the 40 ± 3 torr range.
`
`Intraoperative Studies
`Fluorescein Angiography:The technique of fluores(cid:173)
`cein angiography has been described in detail
`elsewhere. 5 •6 •9 Studies were performed before and after
`anastomosis. Sodium fluorescein (5 ml of a l % solu(cid:173)
`tion) was injected rapidly into the ipsilateral CCA
`through the indwelling catheter. Illumination for
`photography was provided by a strobe light equipped
`with a Kodak-Wratten 47A filter.* Barrier filters
`(Kodak-Wratten 2B and 21) were used to keep un(cid:173)
`wanted exciting radiation from reaching the film.
`Rapid, serial photographs of the cortex were taken
`with a motorized Nikon camera fitted with a 200-mm
`Medical Nikkor lens.t A data-back digital timer:j:
`automatically printed the time in one-hundredths of a
`second in the corner of each frame. The surgeon
`viewed th.e operative field through a presterilized
`Kodak-Wratten 21 filter.
`Xenon-133 Clearanc·e Studies. Clearance studies
`were performed immediately following fluorescein
`angiography, that is, before and after anastomosis.
`
`*Kodak-Wratten 47A filters manufactured by Eastman
`Kodak Co., 3483 State Street, Rochester, New York.
`tNikon camera and Nikkor lens manufactured by Nikon,
`Inc., 623 Stewart Avenue, Garden City, New York.
`:j:Data-back digital timer designed and made in the
`Department of Neurosurgery, Montreal Neurological
`Institute, Montreal, Quebec, Canada.
`
`The cortex was covered with a thin plastic film. Four
`small, lithium-drifted semiconductor detectors were
`placed gently on the plastic film overlying the inferior
`frontal, supramarginal, angular, and superior tem(cid:173)
`poral gyri. Xenon-133 (10 to 12 mCi) dissolved in 3 ml
`of isotonic saline was rapidly injected into the ip(cid:173)
`silateral CCA through the indwelling catheter. The
`detecting system was remotely connected through a
`scalar interface to a PDP-12 computer. The mean
`rCBF from each cortical area was calculated by a
`modification of the stochastic analysis. 5 •10
`
`Results
`Intraoperative Findings
`Gross Observations. Evidence of previous infarc(cid:173)
`tion, consisting of gyral atrophy and pallor, was seen
`in 10 patients. It involved a single gyrus in two
`patients, two or three gyri in six patients, and more
`than three gyri in two patients. In eight of these 10
`patients, cortical infarction was found to lie in the
`territory of a severely sclerotic cortical artery.
`Neovascularization, consisting of numerous irregular,
`thin-walled vessels, was seen adjacent to the infarcted
`areas in 5 patients.
`Fluorescein Angiography. Studies performed
`before anastomosis showed delayed filling of the cor(cid:173)
`tical branches of the MCA. The mean duration
`between injection of fluorescein into the ipsilateral
`CCA and its initial appearance in the epicerebral cir(cid:173)
`culation was 2.4 ± 0.4 seconds, compared with
`0.7 ± 0.3 seconds following anastomosis. In patients
`with occlusive disease of the ICA, filling of the MCA
`branches occurred in an anterograde direction. In the
`patient with high-grade stenosis of the MCA trunk
`(Case 15), filling of the MCA branches occurred in a
`retrograde direction through epicerebral collateral
`channels from the anterior and posterior cerebral
`arteries.
`Patency of the anastomosis was demonstrated in 13
`patients. In one of these patients (Case 13), partial
`obstruction of the ST A was seen at the site where the
`temporary occluding clip had been applied. This was
`corrected by gentle manipulation and the application
`of a small amount ( <; 2 ml) of 1 % Xylocaine
`(lidocaine). The anastomosis was found to be occluded
`in two patients. A thrombus was successfully removed
`and patency restored in one of these patients (Case 6).
`In the other (Case 3), patency was re-established in the
`proximal segment only of the receptor artery. The cor(cid:173)
`tical receptor artery in both patients was narrow ( < 1
`mm) and diffusely atherosclerotic.
`Fluorescein transit time through the ST A was slow
`(> 1.5 seconds) in two patients. One (Case 8) had a
`70% stenosis at the origin of the ECA. The other
`patient (Case 9) had a diffusely narrow ( < 1 mm),
`atherosclerotic ST A.
`Circulation time, that is, time between maximum
`arterial and venous filling, was improved in all
`
`'
`]
`
`562
`
`J. Neurosurg. / Volume 50 / May, 1979
`
`Novadaq Technologies Inc. Exhibit 2001 Page 3
`
`

`

`Intraoperative evaluation of STA-MCA anastomosis
`
`FIG. I. Fluorescein angiography after anastomosis in Case 4. Upper Left: Left temporoparietal
`craniotomy before fluorescein angiography. The superficial temporal artery was covered by a generous cuff
`of connective tissue and fat (X). Upper Right: At 01 : 13 seconds following injection of fluorescein, filling of
`the cortical receptor artery was observed. Center Left: The cortical branches of the middle cerebral artery
`filled in an anterograde direction. The microcirculation supplied by the receptor artery also has
`filled . Center Ri¥ht: Microcirculatory filling :,ivas widespre~d. Lower_ Left_: Filling of cortical veins has
`begun. Lower Right: At 11 : 14 seconds, the vems were well filled and m1croc1rculatory washout was essen(cid:173)
`tially complete. Leakage of fluorescein into the extravascular compartment was seen adjacent to the cortical
`receptor artery.
`
`J. Neurosurg. / Volume 50 / May, 1979
`
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`
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`
`

`

`J. R. Little, Y. L. Yamamoto, W. Feindel, E. Meyer and C. P. Hodge
`
`FIG. 2. Fluorescein angiography after anastomosis in Case 5. Upper Left: Right temporoparietal
`craniotomy before fluorescein angiography. The letters indicate the sites of the 133Xe detectors. Upper
`Right: At 00: 86 seconds following injection of fluorescein, filling of the cortical receptor artery was
`observed. Lower Left: Fluorescein filling was limited predominantly to the receptor artery
`territory. Lower Right: At 04:74 seconds, the veins draining this area filled with fluorescein. Washout in
`the lower gyri was more rapid. Preanastomotic regional blood flow (rCBF), in ml/ 100 gm/min, at the four
`detector sites was: A, I 5; B, I 5; C, 17; and D, 20. Postanastomotic rCBF was: A, 56; B, 33; C, 60; and D, 40.
`
`patients following anastomosis. Comparison of the
`preanastomotic and postanastomotic circulation times
`revealed a mean improvement of 44% (range: 10% to
`80%).
`Fluorescein angiography showed the distribution of
`blood supplied by the ST A through the anastomosis.
`Of the 14 patients who underwent surgery for
`occlusive disease of the ICA, nine had filling of multi(cid:173)
`ple MCA cortical branches (Fig. l) and five had filling
`predominantly in the receptor artery territory (Fig. 2).
`Essentially all of the MCA cortical branches filled in
`an anterograde direction in the patient (Case 15) with
`MCA occlusive disease (Fig. 3).
`
`564
`
`Many of the severely sclerotic cortical arteries were
`occluded and consequently did not fill with fluores(cid:173)
`cein. The cortical microcirculation in their territory
`occasionally filled slowly through multiple irregular,
`thin-walled channels (that is, by neovascularity) com(cid:173)
`ing from adjacent cortical arteries. Impaired micro(cid:173)
`circulatory filling and washout were often seen in
`areas supplied by patent, sclerotic MCA branches
`(Fig. 4). Although these regional flow abnormalities
`persisted after anastomosis, some improvement was
`noted.
`Extravasation of fluorescein out of the microvas(cid:173)
`culature was occasionally observed adjacent to the
`
`J. Neurosurg. / Volume 50 / May, 1979
`
`Novadaq Technologies Inc. Exhibit 2001 Page 5
`
`

`

`Intraoperative evaluation of STA-MCA anastomosis
`
`FIG. 3. Fluorescein angiography after anastomosis in a patient (Case 15) with severe stenosis of the left
`middle cerebral artery (MCA). Upper left: Left temporoparietal craniotomy prior to fluorescein
`angiography. Upper Right: At 01: 37 seconds following injection of fluorescein, filling of the cortical
`receptor artery was observed. Center Left: The MCA cortical branches filled in an anterograde direc(cid:173)
`tion. Center Right: Microcirculatory filling was widespread. Lower Left: Microcirculatory washout and
`early venous filling were seen at 07: 72 seconds. Lower Right: The cortical veins were filled with fluorescein
`at 12: 69 seconds.
`
`anastomotic site. Similar leakage was not seen at
`other locations.
`Xenon-133 Clearance Studies. The results of the
`preanastomotic and postanastomotic studies are listed
`in Table 2. The preanastomotic rCBF values were
`similar (difference ~ 10 ml/100 gm/min) at the four
`recording sites in nine patients. In the others, con(cid:173)
`siderable variation was seen from one recording site to
`
`the next with areas of very low flow (~ 25 ml/100
`gm/min) interspersed with areas of more normal flow
`(~ 40 ml/100 gm/min). Severe reduction of rCBF
`(~ 25 ml/100 gm/min) at one or more recording sites
`was observed in eight patients.
`Immediate, substantial(~ 15 ml/100 gm/min) in(cid:173)
`creases in rCBF were demonstrated following
`anastomosis in 11 patients. In four of them, the im-
`
`J. Neurosurg. / Volume 50 / May, 1979
`
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`
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`
`

`

`J. R. Little, Y. L. Yamamoto, W. Feindel, E. Meyer and C. P. Hodge
`
`. FIG. 4 .. Right temporoparietal craniotomy after anastomosis in Case 9. Left: Severe sclerosis of cor(cid:173)
`tical arteries (arrows) w_as observed. Neovas~ular channels have developed in the vicinity of these diseased
`v_esse)s. The ST A was d1'.fusely atheros~lerot1~ and narrow ( < 1 mm). It was obscured by a cuff of connec(cid:173)
`tive tissue and fat (X). R1g~t: Fluorescem ang1ogram at 08 :29 seconds showed slow arterial fillin
`restricted
`to_ the receptor ar!e~y terntory. The ~cleroti~ cortical artery (arrow) filled poorly, and there !as delayed
`m1cro~1rculatory !iilm!l of the cortex It supplied. Leakage of fluorescein into the wall of the ST A and sur(cid:173)
`rounding connective tissue was noted.
`
`pro~ement was pn~dominantly in the receptor artery
`territory, whereas m the other seven patients, the im(cid:173)
`provement was generalized. The areas with increased
`rCBF did not always correlate with the distribution of
`fluorescein entering
`the epicerebral circulation
`through the ST A.
`Me~n ~mprovem~nt in r~BF was 12 ± 5 ml/100
`gm/mm m the patients with an STA and cortical
`receptor artery greater than 1 mm in diameter. The
`rCBF in~rease ~veraged 7 ± 4 ml/ I 00 gm/min in
`those pa_tlents with an ST A and/ or cortical receptor
`artery diameter of 1 mm or less.
`One patient (Case 10), who showed no increase in
`rCBF, had normal preanastomotic values (52 ± 1
`ml/ 100 g~/min). Another patient (Case 3), with post(cid:173)
`anastomotic occlusion of the distal limb of the recep(cid:173)
`tor artery, was found to have further reduction in
`rCBF in the area it supplied. The rCBF was not im(cid:173)
`proved in the two patients (Cases 8 and 9) with slow
`ST A fluorescein transit.
`
`TABLE 2
`lntraoperative m Xe regional cerebral blood flow (rCBF)
`studies in 15 patients undergoing STA-MCA anastomosis
`
`Time of
`Study
`
`133Xe in rCBF (ml/100 gm/min)
`
`Superior
`Supra-
`Inferior
`Frontal marginal Angular Temporal
`Gyrus
`Gyrus
`Gyrus
`Gyrus
`
`34 ± 12
`preanastomosis
`postanastomosis 41 ± 12
`
`32 ± 12
`37 ± 10
`
`31 ± 11
`41 ± 12
`
`30 ± 9
`42 ± 10
`
`566
`
`Clinical Course
`The n~urological status in the patient (Case 3) with
`the partial~y occluded anastomosis was slightly worse
`po~toperatively. Another patient (Case 7) experienced
`a single TIA consisting of right upper extremity weak(cid:173)
`ness and expressive dysphasia during an episode of
`orthostatic hypotension (systolic blood pressure< 100
`mm Hg). The postoperative angiogram in this patient
`sh_ow~d an occ_luded left ICA instead of a severe supra(cid:173)
`clm01d stenos1_s as demonstrated preoperatively. The
`13 other patients were neurologically unchanged.
`There were no non-neurological complications.
`Patency of the anastomosis was demonstrated on
`the 12 postoperative angiograms performed 10 to 14
`days following surgery. An angiogram was not done
`on the pat_ient (Case 3) with the partially occluded
`anastomosis shown by fluorescein angiography. In(cid:173)
`crease in the luminal diameter of the ST A was
`observed in 11 patients (mean increase: 1.5 ± 0.5
`mm). Filling of multiple MCA branches was seen in
`nine patients. One patient (Case 9) was found to have
`slow filli~g of ~he ST A and cortical receptor artery.
`The lummal diameter of the diffusely narrow ( < 1
`mm), atherosclerotic ST A in this case was unchanged
`from preoperatively.
`All patients are alive 4 to 21 months (mean: 16
`months) following surgery. Symptoms of cerebral
`ischemia have not recurred.
`
`Discussion
`lntraoperative fluorescein angiography and 133Xe
`clearance studies have been used extensively by us in
`
`J. Neurosurg. / Volume 50 / May, 1979
`
`Novadaq Technologies Inc. Exhibit 2001 Page 7
`
`

`

`Intraoperative evaluation of STA-MCA anastomosis
`
`treatment of cerebral arteriovenous
`. the surgical
`malformations, and more recently in STA-MCA
`anastomosis. 5 •12 Information from the studies per(cid:173)
`formed during the revascularization procedure has
`provided valuable insight into anastomotic patency,
`distribution of blood supplied by the ST A, changes in
`epicerebral circulatory patterns, and rCBF. Perma(cid:173)
`nent morbidity related to the use of these techniques
`was not encountered.
`
`Fluorescein Angiography
`Complete evaluation of collateral flow before
`anastomosis would have required catheterization of
`both CCA's and a vertebral artery. The added risk of
`such an investigation and the associated increase in
`surgical and anesthetic time were considered un(cid:173)
`acceptable.
`Patients with ICA occlusive disease were found to
`have slow epicerebral filling and washout. Fluorescein
`injected into the ipsilateral CCA had to pass through
`collateral channels between the ECA and intracranial
`ICA before reaching the MCA branches. Initial filling
`of the cortical arteries consequently was delayed, and
`the concentration of fluorescein diluted. These find(cid:173)
`ings suggested that the collateral supply from this
`source alone was inadequate.
`Filling of the MCA branches before anastomosis
`occurred in an anterograde direction in patients with
`ICA occlusive disease. In the patient with MCA
`stenosis, filling of these branches was in a retrograde
`direction from the anterior and posterior cerebral
`arteries. A similar pattern of retrograde flow has been
`demonstrated in acute embolic MCA occlusion. 7 Such
`a flow pattern is expected when the obstructed artery
`is distal to the circle of Willis, and underscores the
`collateral capacity of the epicerebral connections
`between the three major cerebral arteries.
`Some varia.tion of microcirculatory filling was
`observed. Focal
`impairment of fluorescein
`flow
`usually occurred in the territory of a severely sclerotic
`cortical artery. Adjacent cortex often appeared in(cid:173)
`farcted. Filling of the microcirculation in these areas
`occasionally took place through irregular, thin-walled
`neovascular channels arising from less-diseased cor(cid:173)
`tical arteries. Filling and washout of fluorescein was
`slow but some improvement was observed following
`anastomosis. These findings indicated the importance
`of occlusive disease in the epicerebral arteries in
`patients with ICA or MCA occlusion.
`Using the technique of fluorescein angiography
`described by Feindel, et al., 5 •6 Merei13 performed
`studies on patients undergoing surgery for cerebral
`ischemia caused by thrombosis or stenosis of either
`the ICA or MCA. He described the frequent ex(cid:173)
`travasation of fluorescein from veins in ischemic foci.
`Similar leakage of fluorescein into the extravascular
`compartment was not observed in our study. Some ex(cid:173)
`travasation of fluorescein, however, was seen oc-
`10nally in the vicinity of the anastomotic site. This
`
`was thought to be the result of slight surgical trauma
`and temporary occlusion of the cortical receptor
`,
`artery.
`Verification of anastomotic patency during surgery
`is of utmost importance. Recent experimental studies
`by Rosenbaum and Sundt17 suggest that anastomoses
`which are patent at 30 minutes remain patent
`thereafter. Our findings substantiated this conclusion.
`It is unlikely that patency of the anastomosis can be
`re-established when the STA fails to fill on the post(cid:173)
`operative angiogram unless it is performed shortly
`after surgery. 20 Direct observation of the anastomosis·
`alone can be misleading, as shown in three of our
`patients. All three anastomoses appeared to be func(cid:173)
`tioning well when examined with the operating micro(cid:173)
`scope; however, fluorescein angiography revealed
`thrombosis at the anastomotic site in two and obstruc(cid:173)
`tion of the ST A at the site of temporary clip applica(cid:173)
`tion in one. Satisfactory flow through the anastomosis
`subsequently was achieved in two of them.
`Fluorescein angiography clearly displayed the dis(cid:173)
`tribution of blood entering the epicerebral circulation
`through the ST A. Filling and washout of the micro(cid:173)
`circulation was generally improved. In 67% of
`patients, multiple cortical branches of the MCA filled
`with fluorescein, whereas in 33% only the receptor
`artery and its branches filled. Direction of flow in the
`cortical arteries of the patient with MCA stenosis had
`converted from retrograde to anterograde. The flow
`patterns. observed in the 15 patients were thought to
`reflect the equilibrium established between the pre(cid:173)
`existing collateral input and the newly created arterial
`source.
`
`Xenon-133 Clearance Studies
`The findings before anastomosis were somewhat
`variable, and a uniform pattern of rCBF changes was
`not defined. Multifocal reduction of rCBF, similar to
`that described by Schmiedek, et al., 18 was not demon(cid:173)
`strated consistently but foci of reduced rCBF could
`have been missed as only four detectors were used.
`Multifocal reduction of rCBF was demonstrated in 13
`of our patients studied preoperatively with krypton-77
`positron emission tomography. The results of these
`studies are reported separately. 12,23
`Electroencephalographic
`abnormalities were
`observed by Sundt, et al.,19 when rCBF was acutely
`reduced below 17 to 18 ml/ 100 gm/ min in patients un(cid:173)
`dergoing carotid endarterectomy. Other inves(cid:173)
`tigators2·21·22 have shown experimentally that infarc(cid:173)
`tion occurs if these low rCBF levels persist. In 55% of
`our patients, rCBF was reduced to 25 ml/ 100 gm/min
`or less at one or more detector sites.
`The rCBF values invariably were below 25 ml/ 100
`gm/min in areas supplied by severely sclerotic cortical
`arteries. It is not surprising that the adjacent cortex
`frequently had changes indicative of previous infarc(cid:173)
`tion. The presence of occlusive disease of the cortical
`arteries could be an important factor in producing the
`
`Neurosurg. / Volume 50 / May, 1979
`
`567
`
`Novadaq Technologies Inc. Exhibit 2001 Page 8
`
`

`

`J. R. Little, Y. L. Yamamoto, W. Feindel, E. Meyer and C. P. Hodge
`
`multifocal pattern of ischemia described in other
`reports. 12, 1s,2a
`Improvement in rCBF was demonstrated in 73% of
`patie.nts following anastomosis. Increased rCBF was
`not confined to the territory of the receptor artery in
`most patients. Mean rCBF increases were comparable
`at the four detector sites. Improvement in rCBF was
`frequently seen in areas supplied by sclerotic cortical
`arteries, although it tended to be less pronounced than
`in areas supplied by normal-appearing arteries.
`Failure to improve rCBF resulted from thrombosis at
`the anastomotic site, diffuse atherosclerotic narrow(cid:173)
`ing of the STA or cortical receptor artery, or focal
`stenosis of the ECA. In one patient, normal rCBF
`values before anastomosis were unchanged post(cid:173)
`operatively.
`The rCBF was consistently better in patients with
`donor and receptor arteries greater than 1 mm in
`diameter. Chater4 has reported similar findings. Using
`a flowmeter attached to the ST A during surgery, he
`showed a mean flow of 37 ± 15 ml/min in patients
`with arteries greater than 1 mm in diameter. Those
`patients with one or both arteries measuring 1 mm or
`less in diameter had a mean flow of 18 ± 8 ml/min.
`These findings stress the importance of utilizing the
`largest arteries available when performing the
`anastomosis.
`Some incongruities between the findings of post(cid:173)
`anastomotic fluorescein angiography and 133Xe
`clearance studies were seen. Substantial increases in
`rCBF were occasionally demonstrated in areas with
`little or no fluorescein filling. Arterial blood supplying
`these areas likely was derived from epicerebral
`collaterals from the anterior and posterior cerebral
`arteries as well as deeper cortical layers and subcor(cid:173)
`tical white matter not visualized by fluorescein
`angiography. Collateral flow in these areas could be
`identified, however, by determining the clearance of
`the gamma-emitting 133Xe. The 133Xe clearance curves
`indicated a redistribution of blood flowing into the
`epicerebral circulation, resulting in improvement in
`rCBF that was more widespread than was evident with
`fluorescein angiography alone.
`
`Clinical Considerations
`Our clinical results substantiate previously reported
`studies indicating that STA-MCA anastomosis im(cid:173)
`proves the natural history of selected patients suffer(cid:173)
`ing from cerebrovascular occlusive disease. 3•8• 20•25 The
`findings of this study suggest that improved cerebral
`perfusion is an important factor in the prevention of
`cerebral infarction in these patients.
`
`Acknowledgments
`
`The authors would like to express appreciation to the
`neurosurgical residents and operating room staff for their in(cid:173)
`valuable contribution to this investigation. Fluorescein
`angiography was performed with the generous and able
`assistance of Miss Judith Little and Mr. Marcus Arts.
`
`568
`
`References
`1. Austin G, Hayward W, Laffin D: Use of cerebral blood
`flow for selection and monitoring of patients, in Austin
`GM (ed): Microneurosurgical Anastomoses for Cerebral
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`1974
`3. Chater N: Patient selection and results of extra- to in(cid:173)
`tra-cranial anastomosis in selected cases of cerebrovas(cid:173)
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