Aust. Radiol. (1975). 19, 152
Radionuclide Studies of Regional Cerebral Perfusion: Extended Computer Analysis of Anterior and Middle Cerebral Artery Circulation R. J. ~ R E I L LB.Sc., Y , M.A.I.P., P. J. COLLINS, B.TEcH. (APPLIED PHYSICS), AND P. M. RONAI,B.Sc., M.B., B.S., PH.D.
Division of Nuclear Medicine, Institute of Medical and Veterinary Science, Adelaide INTRODUCTION The use of a "non-diffusible" tracer, technetium-99m pertechnetate, for detection of regional perfusion abnormalities of the brain in patients with cerebrovascular disease is now firmly established (Oldendorf and Kitano, 1967; Maynard et al., 1969; Rosenthall and Martin, 1970; Moses et al., 1972). Rapid sequence srintiphotography with the gamma camera following a bolus injection of ""mT~O,-can detect perfusion abnormalities resulting from the occlusion of major cerebral blood vessels such as the internal carotid or middle cerebral arteries. However, perfusion abnormalities due to vascular occlusion distal to the major arteries are not readily detected by such simple analogue techniques. One reason for this is that inherent non-uniformities in gamma camera detector sensitivity produce count-rate variations of the same order as those caused by many perfusion abnormalities. Accordingly, non-uniformity correction is an essential pre-requisite to the sensitive detection of less than major perfusion abnormalities. At the present time, non-uniformity correction can be accomplished only by digital techniques (OReilly et al., 1972; Moses et al., 1973; Collins et al., 1973). Digital processing of dynamic cerebral radioangiographic data to detect regional perfusion abnormalities requires delineation of regions for analysis. This can be accomplished on commercial equipment by dialling of matrix co-ordinates or by light pen during data playback onto a CRT display. Both these methods suffer from the disadvantages of poor reproducibility and inconstant relationship to the superior sagittal sinus and head outline. A more reproducible and -rate technique for delineating regions of interest using automatic sequences of statistical operations performed by computer has been described 152
(OReilly et a[., 1972). This has proved of particular value in analysis of a large number of digital cerebral radioangiograms for small perfusion abnormalities in patients with suspected occlusive cerebrovascular disease. This technique has also been used to detect vascular spasm following subarachnoid haemorrhage (Ronai et al., 1973). Since aneurysms of the anterior cerebral and anterior communicating arteries are more common than aneurysms of the middle cerebral arteries, it has been found advantageous to extend the previously described computer programme to select not only areas corresponding with the distribution of left and right middle cerebral arteries, but also an area corresponding with the proximal portion of both anterior cerebral arteries. METHOD A detailed description of the method used for recording the cerebral radioangiogram and analysing perfusion in regions representing predominantly the distribution of the middle cerebral arteries has been previously reported (OReilly et al., 1972). In brief, the patient is positioned supine with the collimator face of a Pho/Gamma 111 scintillation camera at right angles to the orbito-meatal plane of the patient's head. Approximately 15 mCi of gDmTc-pertechnetate are injected intravenously using a bolus injection technique. Rapid sequence scintiphotos, each of two seconds exposure, are recorded on 35 mm film using a 35 mm camera with motor drive, and digital data are recorded (via dual analogue-to-digital converters, a 1600 channel multiparameter analyser and 7 track digital recorder) on magnetic tape. Twenty-five consecutive frames each of 1.8 seconds digital data storage time are recorded. Computer analysis is performed off-line using the university of Adelaide's CDC 6400 computer. The Australasian Radiology, Vol. X I X , N o . 2 , June, 1975
RADIONUCLIDE STUDIES OF REGIONAL CEREBRAL PERFUSION
computer programme performs the following functions: ( 1 ) Filtering and smoothing; ( 2 ) Non-uniformity correction; (3) Automatic region-of-interest selection; (4) Region-of-interest area nOllIlaliSatiOn; ( 5 ) Printing by line printer of histograms of total corrected counts per normalised region-of-interest per unit time, together
with print-out of the difference between left and right regions-of-interest counts (expressed in standard deviations) at each data point; (6) Plotting of curves from histogram data by Calcomp X-Y plotter. Region-of-interest selection is based on the cumulative digital "image" of the head, representing the cerebral vascular pools (Figure 1 ). Transverse and longitudinal digital profiles
Australmian Radiology. Vol. XIX. N o . 2, June. 1975
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R.J. OREILLY AND P. M. RONIA
FIGURE 2-Longitudinal profile. Plotted from the partcolumn sums in the midline strip. Superior sagittal sinus peak (A) and the trough corresponding to the interhemispheric region (B).
are constructed from the cumulative digital ‘‘irpge.’’ From the transverse profile, a midline stnp is selected whose lateral boundaries enclose the superior sagittal sinus. The boundaries of this midline strip are refined by iterative steps in the programme to avoid errors due to the presence of abnormal vascular pools. A longitudinal profile (Figure 2) is plotted from the part-column sums in this midline strip and from this longitudinal profile the top of the head and the boundary between brain and nasopharynx are determined. The lateral boundaries of the head are determined by scanning individual rows to detect the first sigeificant deviation from background. Two quadrant-shaped regions are thus delineated with a midline strip between them encompassing the superior
sagittal sinus (Figure 1) . The quadrant-shaped regions correspond roughly with the middle cerebral artery territories. The anterior cerebral artery territory is derived from the midline strip as follows: From the longitudinal profile plotted from the midline strip, the difference (D,) between the maximum partcolumn sum-corresponding to the superior sagittal sinus peak (A in Figure 2)-and the mean (M,) of the six minimum values of partcolumn sums in the trough (B in Figure 2) caudal to the sagittal sinus peak is calculated. The first part-column sum moving from this trough towards the top of the head which has a value greater than M, 0.3 D, is taken to represent the superior boundary of the anterior cerebral territory. The
154
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RADIONUCLIDE STUDIES OF REGIONAL CEREBRAL PERFUSION
FIGURE3-Three superimposed h i s t o m of the intezrated counts per time segment versus time for the three regions L, R and A. The statistical difference between L and R is printed directly beneath each data point alternately in the fist two l i e s under the plot. The statistical difference between A and the greater of L and R are printed in the second pair of lines. The above analysis is within normal limits.
inferior boundary has the same coordinate as the inferior boundary of the middle cerebral regions. Three regions-of-interest are thus delineated: Two quadrant-shaped regions each Corresponding approximately with the temtory of one middle cerebral artery as seen on the anterior projection, and one midline region corresponding with the proximal portion of both anterior cerebral arteries. These three regions are of course individually selected by the computer for each patient. To compile the histograms, counts are integrated within each of the three regions-ofinterest for each of the 25 frames of the study. Integrated counts in the two middle cerebral regions are normalised to the average area of the two middle cerebral regions to compensate
for unequal size of these regions due to rotation or asymmetry of the head. Integrated counts in the anterior cerebral region are normalised by a factor of 4/AA where A A is the area of the anterior region. This normalising factor was found empirically to facilitate plotting of the histogram for the anterior cerebral region on the same axes as the histograms for the middle cerebral regions. The three superimposed histograms are printed using a line printer (Figure 3). To improve the sensitivity of the plot, the difference between left and right middle cerebral histograms at each data point is calculated and expressed in standard deviations. Also the difference between the left or right middle cerebral histogram (whichever is greater) and the anterior cerebral histogram is calculated and also expressed in standard devia-
Australasian Radiology, Vol. XIX,No. 2, June. 1975
155
R.J. OREILLY AND P. M. RONIA tions for each data point. These figures are printed directly beneath the appropriate data points on the plot. An additional output on Calcomp X-Y plotter is produced for inclusion in the report to the referring doctor.
FLOWPATTERN THENORMAL Normally, left and right middle cerebra1 histograms are equal throughout the plot. The flow pattern in the anterior cerebral region is more complex in its relationship to the other histograms. In order to characterise the anterior cerebral flow pattern, the difference (in S.D.s) between the anterior region counts and the greater of the left or right region counts was plotted for each of 220 consecutive patients (without clinical or static brain scan grounds for suspecting abnormalities in cerebral perfusion). Distributions were obtained for differences at three points on each histogram:( 1 ) the midpoint of the ascending phase ( 2 ) the peak ( 3 ) the equilibrium or plateau phase The three distributions (Figure 4) have means at -2.5, -2.1 and +4.2 S.D.s respectively . The analysis of all three regions is now routinely performed on radioangiograms of all patients referred for brain scans. The extensions to the computer programme have not significantly increased either the processing time or the cost.
nu*
-
-2.l 2.9
*ELM
-2.5
c
1.7.
L 2 4 6 8 DIFFEPLNCE
VhIUES
FIGURE T '.he distributions of the statistical difference values at the mid-point ascending, peak and plateau phases from 220 patients without clinical grounds for suspecting abnormalities in cerebral perfusion.
RESULTS Figure 3 is a normal digitai cerebral radioangiogram from a patient without clinical evidence of occlusive cerebrovascular disease. The left and right histograms are equal as indicated by the low significance of the difference values tabulated in the first two lines bAow the plot. The difference values for the anterior histogram tabulated in lines 3 and 4 are a mean of - 2.8 at the midpoint of the ascending phase, -3.1 at the peak and a mean of 3.0 at the plateau. These values are close to the normal means of - 2.5, - 2.1 and 4.2, respectively. Figure 5 shows a digital cerebral radioangiogram from a 56-year-old male who had had an anterior communicating aneurysm clipped five days before. He had not regained consciousness postoperatively. The anterior region shows difference readings of +4.4 at both midpoint of ascending phase and peak. These are respectively 4.1 and 3.3 standard deviations from the
normal values at these points. A progress study recorded six weeks later when the patient had improved clinically is shown in Figure 6. The clinical improvement is paralleled by improvement in anterior region flow which is now at the normal value at the mid point and 2.0 standard deviations from the normal value at the peak. The difference values for the anterior region plot need to be interpreted with care when there are perfusion abnormalities due to hyperperfused lesions in either hemisphere. Figure 7 shows the analogue cerebral radioangiogram of a 9-year-old girl with an arteriovenous malformation in the left frontal region. Figure 8 is the simultaneously recorded digital study. Because the difference values for the anterior region are obtained by comparison of the anterior region with whichever is greater of the left and right region plots, the calculated difference
156
Australasian Radiology, Vol. X l X , No. 2, June, 1975
+
+
RADIONUCLIDE STUDIES OF
FIGURE 5-Digital
REGIONAL CEREBRAL PERFUSION
perfusion study showing a greatly decreased perfusion in the anterior cerebral repion.
values for the anterior region in this patient clinical grounds for suspecting abnormalities in indicate greatly decreased perfusion in the an- cerebral perfision. The resulting normal A plot terior region. It is clear from correlation of parameters were then used as a basis for assessanalogue and digital results that the greater ing the normality or otherwise of A plots in plot (in this case the left) is the abnormal one, patients with suspected occlusive cerebrovasand hence d ~ e r e n c evalues for the anterior cular disease. In relating A to the greater of L region calculated from the left region plot are or R, the assumption was made that if L and R are unequal, the greater of the two is normal spurious. and the smaller abnormal. This holds in occluDISCUSSION sive cerebrovascular disease during the arterial The normal pattern in the anterior region phase (but not necessarily in the venous phase (A) does not bsar a 1:1 ratio to the pattern in where a “flip-flop” pattern would reverse this either left or right region (L or R). Indeed, relationship). However, in the case of vascular because the normalising factor is chosen so space-occupying lesions (e.g. vascular n e e that A can be plotted on the same set of axes plasms, arterio-venous malformations and large as L and R, any plot of A bears a rather aneurysms) in the L or R region, the greater of arbitrary relationship to L and R.Accordingly, the two plots is the abnormal one. In practice, in order to determine the normal A plot, the correlation of clinical data, static and dynamic relationship between A and L (or R ) was de- scintiphotos and computer output avoids the termined in a series of 220 patients without possibility of confusion. Australasian Radiology,
Vol. XIX. No. 2, June, 1975
157
R.J. OREILLY AND P.M.RONU
FIGURE &Digital perfusion study of the same patient as in Figure 5 showing a markedly improved circulation in the anterior cerebral region.
haemorrhage, it has bzen advantageous to analyse not only the left and right middle cerebral artery territories but also the anterior cerebral artery temtory, since aneurysms of the anterior cerebral and anterior communicating arteries are the most common. This paper describes a simple extension to the computer programme used in this laboratory for selecting left and right middle cerebral artery regions-of-interest to allow a third region-ofinterest over the proximal portions of the two anterior cerebral arteries to be selected. The programme enables the perfusion histogram for the anterior cerebral region (A) to be printed on the same axes as the perfusion histograms for the left and right middle cerebral regions SUMMARY (Land R). The normal A plot has been characterised In using the digital cerebral radioangiogram to detect vascular spasm due to subarachnoid by evaluating the difference (in standard devia-
Although the computer programme is able to avoid abnormal blood pools in the two hemicrania when selecting L or R regions (see Ref. 1 ), any such pool in the anterior region could result in foreshortening of the region selected. Large aneurysms of the anterior cerebral or anterior communicating arteries usually produce this effect. In this case, the anterior region does not include the aneurysm itself, but extends from the aneurysm distally. Inclusion of a large aneurysm in the anterior region would actually be a disadvantage since detection of spasm in the vessel distal to the aneurysm would bz hindered by including the relatively large vascular pool of the aneurysm in the analysis.
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Australasian Radiology, Vol. XIX, No. 2, June, 1975
RADIONUCLIDE STUDIES OF
REGIONAL aREBRllL
PERFUSION
FIGURE 7-Analogue cerebral radioaasiogram showing the internal carotid, middle cerebral and anterior cerebral vessels. A large arteriovenous malformation (dark area) is seen in the left frontal r e o n on the right of the figure.
tions) between A counts and L or R counts (whichever is greater) at three points (midpoint of ascending phase, peak and plateau phase) on each histogram in 220 patients without clinical grounds for suspecting abnormalities in cerebral perfusion. An example is shown of an abnormal A plot in a patient with anterior cerebral artery spasm following surgery for an anterior communicating aneurysm; and a further exam-ole of a normal A plot which could
be spuriouslyjudged abnormal by the statistical analysis as a result of comparing perfusion in the A region with an abnormally hyperperfused L region containing an AV malformation. Correlation of clinical data and static and dynamic scintiphotos with the computer output is needed to avoid such errors of interpretation. The tendency of the computer programme to exclude abnormal vascular pools from the anterior region facilitates detection of spasm dis-
Australasian Radiology. Vol. XIX,'No. 2, June, 1975
159
€2. J. OREILLY AND P. M. RONU
FIGURE &-Digital perfusion study recorded simultaneously with the study of Figure 7. The statistical difference values in both pairs of rows are abnormal. However, the anterior circulation is normal as would have been shown If drfference values had been computed agamst the normal perfusion of the right hemisphere.
tal to an anterior cerebral or anterior com- ‘Moses, D. C., Natarajan, T. K., Previosi, T. J., Udvarhelyi, G. B. and Wagner, H. N., Jr.. (1973): municating aneurysm since a large aneurysm “Quantitative Cerebral Circulation Studies with would itself be excluded from the region Sodium Pertechnetate.” I. Nucl. Med., 14, 142. analysed. ‘Oldendorf, W. H. and Kitano, M. (1967): “Radio‘Collins, P. J., OReilly, R. J. and Ronai, P. M.(1973): “Spatial Non-Umformty m Detector Sensitivity of a Gamma Camera: Detection, Minimization and Correction.” Aurt. & NZ. I . Med., 3, 526 (Abstract). ‘Maynard, C. D., Witcofski, R. L., Janeway, R. and Cowan, R. J. (1969): “Radioisotope Arterie graphy as an Adjunct to the Brain Scan.” Radiology, 92, 908. ‘Moses, D. C., James, A. E., Straw, H. W. and Wagner, H. N., Jr. (1972): “Regional Cerebral Blood Flow Estimation in the Diagnosis of Cerebrovascular Disease.” I. Nucl. Med., 13, 135.
isotope Measurement of Brain Blood Turnover Time as a Clinical Index of Brain Circulation.” I. Nucl. Med., 8, 570. ‘OReilly, R. J., Cooper, R. E. M. and Ronai, P. M. (1972): “Automatic Computer Analysis of Digital Dynamic Radionuclide Studies of the Cerebral Circulation.” I. Nucl. Med., 13, 658. ’Ronai, P: M., O’Reilly, R. J., Perrett, L. V. and Dmrung, T. A. R. (1973): “The Clinical Role of the Cerebral Radioangiogram: I1 Cerebrovascular Spasm in Subarachnoid Haemorrhage-A Model for Focal Occlusive Cerebrovascular Disease.” Aust. & N.Z. I . Med.. 3,530 (Abstract). *Rosenthall, L. and Martin, R. H. (1970): “Cerebral Transit of Pertechnetate Given Intravenously.” Radiology, 94, 521.
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REFERENCES
Radionuclide Studies of Regional Cerebral Perfusion: Extended Computer Analysis of Anterior and Middle Cerebral Artery Circulation R. J. ~ R E I L LB.Sc., Y , M.A.I.P., P. J. COLLINS, B.TEcH. (APPLIED PHYSICS), AND P. M. RONAI,B.Sc., M.B., B.S., PH.D.
Division of Nuclear Medicine, Institute of Medical and Veterinary Science, Adelaide INTRODUCTION The use of a "non-diffusible" tracer, technetium-99m pertechnetate, for detection of regional perfusion abnormalities of the brain in patients with cerebrovascular disease is now firmly established (Oldendorf and Kitano, 1967; Maynard et al., 1969; Rosenthall and Martin, 1970; Moses et al., 1972). Rapid sequence srintiphotography with the gamma camera following a bolus injection of ""mT~O,-can detect perfusion abnormalities resulting from the occlusion of major cerebral blood vessels such as the internal carotid or middle cerebral arteries. However, perfusion abnormalities due to vascular occlusion distal to the major arteries are not readily detected by such simple analogue techniques. One reason for this is that inherent non-uniformities in gamma camera detector sensitivity produce count-rate variations of the same order as those caused by many perfusion abnormalities. Accordingly, non-uniformity correction is an essential pre-requisite to the sensitive detection of less than major perfusion abnormalities. At the present time, non-uniformity correction can be accomplished only by digital techniques (OReilly et al., 1972; Moses et al., 1973; Collins et al., 1973). Digital processing of dynamic cerebral radioangiographic data to detect regional perfusion abnormalities requires delineation of regions for analysis. This can be accomplished on commercial equipment by dialling of matrix co-ordinates or by light pen during data playback onto a CRT display. Both these methods suffer from the disadvantages of poor reproducibility and inconstant relationship to the superior sagittal sinus and head outline. A more reproducible and -rate technique for delineating regions of interest using automatic sequences of statistical operations performed by computer has been described 152
(OReilly et a[., 1972). This has proved of particular value in analysis of a large number of digital cerebral radioangiograms for small perfusion abnormalities in patients with suspected occlusive cerebrovascular disease. This technique has also been used to detect vascular spasm following subarachnoid haemorrhage (Ronai et al., 1973). Since aneurysms of the anterior cerebral and anterior communicating arteries are more common than aneurysms of the middle cerebral arteries, it has been found advantageous to extend the previously described computer programme to select not only areas corresponding with the distribution of left and right middle cerebral arteries, but also an area corresponding with the proximal portion of both anterior cerebral arteries. METHOD A detailed description of the method used for recording the cerebral radioangiogram and analysing perfusion in regions representing predominantly the distribution of the middle cerebral arteries has been previously reported (OReilly et al., 1972). In brief, the patient is positioned supine with the collimator face of a Pho/Gamma 111 scintillation camera at right angles to the orbito-meatal plane of the patient's head. Approximately 15 mCi of gDmTc-pertechnetate are injected intravenously using a bolus injection technique. Rapid sequence scintiphotos, each of two seconds exposure, are recorded on 35 mm film using a 35 mm camera with motor drive, and digital data are recorded (via dual analogue-to-digital converters, a 1600 channel multiparameter analyser and 7 track digital recorder) on magnetic tape. Twenty-five consecutive frames each of 1.8 seconds digital data storage time are recorded. Computer analysis is performed off-line using the university of Adelaide's CDC 6400 computer. The Australasian Radiology, Vol. X I X , N o . 2 , June, 1975
RADIONUCLIDE STUDIES OF REGIONAL CEREBRAL PERFUSION
computer programme performs the following functions: ( 1 ) Filtering and smoothing; ( 2 ) Non-uniformity correction; (3) Automatic region-of-interest selection; (4) Region-of-interest area nOllIlaliSatiOn; ( 5 ) Printing by line printer of histograms of total corrected counts per normalised region-of-interest per unit time, together
with print-out of the difference between left and right regions-of-interest counts (expressed in standard deviations) at each data point; (6) Plotting of curves from histogram data by Calcomp X-Y plotter. Region-of-interest selection is based on the cumulative digital "image" of the head, representing the cerebral vascular pools (Figure 1 ). Transverse and longitudinal digital profiles
Australmian Radiology. Vol. XIX. N o . 2, June. 1975
153
R.J. OREILLY AND P. M. RONIA
FIGURE 2-Longitudinal profile. Plotted from the partcolumn sums in the midline strip. Superior sagittal sinus peak (A) and the trough corresponding to the interhemispheric region (B).
are constructed from the cumulative digital ‘‘irpge.’’ From the transverse profile, a midline stnp is selected whose lateral boundaries enclose the superior sagittal sinus. The boundaries of this midline strip are refined by iterative steps in the programme to avoid errors due to the presence of abnormal vascular pools. A longitudinal profile (Figure 2) is plotted from the part-column sums in this midline strip and from this longitudinal profile the top of the head and the boundary between brain and nasopharynx are determined. The lateral boundaries of the head are determined by scanning individual rows to detect the first sigeificant deviation from background. Two quadrant-shaped regions are thus delineated with a midline strip between them encompassing the superior
sagittal sinus (Figure 1) . The quadrant-shaped regions correspond roughly with the middle cerebral artery territories. The anterior cerebral artery territory is derived from the midline strip as follows: From the longitudinal profile plotted from the midline strip, the difference (D,) between the maximum partcolumn sum-corresponding to the superior sagittal sinus peak (A in Figure 2)-and the mean (M,) of the six minimum values of partcolumn sums in the trough (B in Figure 2) caudal to the sagittal sinus peak is calculated. The first part-column sum moving from this trough towards the top of the head which has a value greater than M, 0.3 D, is taken to represent the superior boundary of the anterior cerebral territory. The
154
Ausiralasian Radiology, Vol. XIX,No. 2, June, 1975
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RADIONUCLIDE STUDIES OF REGIONAL CEREBRAL PERFUSION
FIGURE3-Three superimposed h i s t o m of the intezrated counts per time segment versus time for the three regions L, R and A. The statistical difference between L and R is printed directly beneath each data point alternately in the fist two l i e s under the plot. The statistical difference between A and the greater of L and R are printed in the second pair of lines. The above analysis is within normal limits.
inferior boundary has the same coordinate as the inferior boundary of the middle cerebral regions. Three regions-of-interest are thus delineated: Two quadrant-shaped regions each Corresponding approximately with the temtory of one middle cerebral artery as seen on the anterior projection, and one midline region corresponding with the proximal portion of both anterior cerebral arteries. These three regions are of course individually selected by the computer for each patient. To compile the histograms, counts are integrated within each of the three regions-ofinterest for each of the 25 frames of the study. Integrated counts in the two middle cerebral regions are normalised to the average area of the two middle cerebral regions to compensate
for unequal size of these regions due to rotation or asymmetry of the head. Integrated counts in the anterior cerebral region are normalised by a factor of 4/AA where A A is the area of the anterior region. This normalising factor was found empirically to facilitate plotting of the histogram for the anterior cerebral region on the same axes as the histograms for the middle cerebral regions. The three superimposed histograms are printed using a line printer (Figure 3). To improve the sensitivity of the plot, the difference between left and right middle cerebral histograms at each data point is calculated and expressed in standard deviations. Also the difference between the left or right middle cerebral histogram (whichever is greater) and the anterior cerebral histogram is calculated and also expressed in standard devia-
Australasian Radiology, Vol. XIX,No. 2, June. 1975
155
R.J. OREILLY AND P. M. RONIA tions for each data point. These figures are printed directly beneath the appropriate data points on the plot. An additional output on Calcomp X-Y plotter is produced for inclusion in the report to the referring doctor.
FLOWPATTERN THENORMAL Normally, left and right middle cerebra1 histograms are equal throughout the plot. The flow pattern in the anterior cerebral region is more complex in its relationship to the other histograms. In order to characterise the anterior cerebral flow pattern, the difference (in S.D.s) between the anterior region counts and the greater of the left or right region counts was plotted for each of 220 consecutive patients (without clinical or static brain scan grounds for suspecting abnormalities in cerebral perfusion). Distributions were obtained for differences at three points on each histogram:( 1 ) the midpoint of the ascending phase ( 2 ) the peak ( 3 ) the equilibrium or plateau phase The three distributions (Figure 4) have means at -2.5, -2.1 and +4.2 S.D.s respectively . The analysis of all three regions is now routinely performed on radioangiograms of all patients referred for brain scans. The extensions to the computer programme have not significantly increased either the processing time or the cost.
nu*
-
-2.l 2.9
*ELM
-2.5
c
1.7.
L 2 4 6 8 DIFFEPLNCE
VhIUES
FIGURE T '.he distributions of the statistical difference values at the mid-point ascending, peak and plateau phases from 220 patients without clinical grounds for suspecting abnormalities in cerebral perfusion.
RESULTS Figure 3 is a normal digitai cerebral radioangiogram from a patient without clinical evidence of occlusive cerebrovascular disease. The left and right histograms are equal as indicated by the low significance of the difference values tabulated in the first two lines bAow the plot. The difference values for the anterior histogram tabulated in lines 3 and 4 are a mean of - 2.8 at the midpoint of the ascending phase, -3.1 at the peak and a mean of 3.0 at the plateau. These values are close to the normal means of - 2.5, - 2.1 and 4.2, respectively. Figure 5 shows a digital cerebral radioangiogram from a 56-year-old male who had had an anterior communicating aneurysm clipped five days before. He had not regained consciousness postoperatively. The anterior region shows difference readings of +4.4 at both midpoint of ascending phase and peak. These are respectively 4.1 and 3.3 standard deviations from the
normal values at these points. A progress study recorded six weeks later when the patient had improved clinically is shown in Figure 6. The clinical improvement is paralleled by improvement in anterior region flow which is now at the normal value at the mid point and 2.0 standard deviations from the normal value at the peak. The difference values for the anterior region plot need to be interpreted with care when there are perfusion abnormalities due to hyperperfused lesions in either hemisphere. Figure 7 shows the analogue cerebral radioangiogram of a 9-year-old girl with an arteriovenous malformation in the left frontal region. Figure 8 is the simultaneously recorded digital study. Because the difference values for the anterior region are obtained by comparison of the anterior region with whichever is greater of the left and right region plots, the calculated difference
156
Australasian Radiology, Vol. X l X , No. 2, June, 1975
+
+
RADIONUCLIDE STUDIES OF
FIGURE 5-Digital
REGIONAL CEREBRAL PERFUSION
perfusion study showing a greatly decreased perfusion in the anterior cerebral repion.
values for the anterior region in this patient clinical grounds for suspecting abnormalities in indicate greatly decreased perfusion in the an- cerebral perfision. The resulting normal A plot terior region. It is clear from correlation of parameters were then used as a basis for assessanalogue and digital results that the greater ing the normality or otherwise of A plots in plot (in this case the left) is the abnormal one, patients with suspected occlusive cerebrovasand hence d ~ e r e n c evalues for the anterior cular disease. In relating A to the greater of L region calculated from the left region plot are or R, the assumption was made that if L and R are unequal, the greater of the two is normal spurious. and the smaller abnormal. This holds in occluDISCUSSION sive cerebrovascular disease during the arterial The normal pattern in the anterior region phase (but not necessarily in the venous phase (A) does not bsar a 1:1 ratio to the pattern in where a “flip-flop” pattern would reverse this either left or right region (L or R). Indeed, relationship). However, in the case of vascular because the normalising factor is chosen so space-occupying lesions (e.g. vascular n e e that A can be plotted on the same set of axes plasms, arterio-venous malformations and large as L and R, any plot of A bears a rather aneurysms) in the L or R region, the greater of arbitrary relationship to L and R.Accordingly, the two plots is the abnormal one. In practice, in order to determine the normal A plot, the correlation of clinical data, static and dynamic relationship between A and L (or R ) was de- scintiphotos and computer output avoids the termined in a series of 220 patients without possibility of confusion. Australasian Radiology,
Vol. XIX. No. 2, June, 1975
157
R.J. OREILLY AND P.M.RONU
FIGURE &Digital perfusion study of the same patient as in Figure 5 showing a markedly improved circulation in the anterior cerebral region.
haemorrhage, it has bzen advantageous to analyse not only the left and right middle cerebral artery territories but also the anterior cerebral artery temtory, since aneurysms of the anterior cerebral and anterior communicating arteries are the most common. This paper describes a simple extension to the computer programme used in this laboratory for selecting left and right middle cerebral artery regions-of-interest to allow a third region-ofinterest over the proximal portions of the two anterior cerebral arteries to be selected. The programme enables the perfusion histogram for the anterior cerebral region (A) to be printed on the same axes as the perfusion histograms for the left and right middle cerebral regions SUMMARY (Land R). The normal A plot has been characterised In using the digital cerebral radioangiogram to detect vascular spasm due to subarachnoid by evaluating the difference (in standard devia-
Although the computer programme is able to avoid abnormal blood pools in the two hemicrania when selecting L or R regions (see Ref. 1 ), any such pool in the anterior region could result in foreshortening of the region selected. Large aneurysms of the anterior cerebral or anterior communicating arteries usually produce this effect. In this case, the anterior region does not include the aneurysm itself, but extends from the aneurysm distally. Inclusion of a large aneurysm in the anterior region would actually be a disadvantage since detection of spasm in the vessel distal to the aneurysm would bz hindered by including the relatively large vascular pool of the aneurysm in the analysis.
158
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RADIONUCLIDE STUDIES OF
REGIONAL aREBRllL
PERFUSION
FIGURE 7-Analogue cerebral radioaasiogram showing the internal carotid, middle cerebral and anterior cerebral vessels. A large arteriovenous malformation (dark area) is seen in the left frontal r e o n on the right of the figure.
tions) between A counts and L or R counts (whichever is greater) at three points (midpoint of ascending phase, peak and plateau phase) on each histogram in 220 patients without clinical grounds for suspecting abnormalities in cerebral perfusion. An example is shown of an abnormal A plot in a patient with anterior cerebral artery spasm following surgery for an anterior communicating aneurysm; and a further exam-ole of a normal A plot which could
be spuriouslyjudged abnormal by the statistical analysis as a result of comparing perfusion in the A region with an abnormally hyperperfused L region containing an AV malformation. Correlation of clinical data and static and dynamic scintiphotos with the computer output is needed to avoid such errors of interpretation. The tendency of the computer programme to exclude abnormal vascular pools from the anterior region facilitates detection of spasm dis-
Australasian Radiology. Vol. XIX,'No. 2, June, 1975
159
€2. J. OREILLY AND P. M. RONU
FIGURE &-Digital perfusion study recorded simultaneously with the study of Figure 7. The statistical difference values in both pairs of rows are abnormal. However, the anterior circulation is normal as would have been shown If drfference values had been computed agamst the normal perfusion of the right hemisphere.
tal to an anterior cerebral or anterior com- ‘Moses, D. C., Natarajan, T. K., Previosi, T. J., Udvarhelyi, G. B. and Wagner, H. N., Jr.. (1973): municating aneurysm since a large aneurysm “Quantitative Cerebral Circulation Studies with would itself be excluded from the region Sodium Pertechnetate.” I. Nucl. Med., 14, 142. analysed. ‘Oldendorf, W. H. and Kitano, M. (1967): “Radio‘Collins, P. J., OReilly, R. J. and Ronai, P. M.(1973): “Spatial Non-Umformty m Detector Sensitivity of a Gamma Camera: Detection, Minimization and Correction.” Aurt. & NZ. I . Med., 3, 526 (Abstract). ‘Maynard, C. D., Witcofski, R. L., Janeway, R. and Cowan, R. J. (1969): “Radioisotope Arterie graphy as an Adjunct to the Brain Scan.” Radiology, 92, 908. ‘Moses, D. C., James, A. E., Straw, H. W. and Wagner, H. N., Jr. (1972): “Regional Cerebral Blood Flow Estimation in the Diagnosis of Cerebrovascular Disease.” I. Nucl. Med., 13, 135.
isotope Measurement of Brain Blood Turnover Time as a Clinical Index of Brain Circulation.” I. Nucl. Med., 8, 570. ‘OReilly, R. J., Cooper, R. E. M. and Ronai, P. M. (1972): “Automatic Computer Analysis of Digital Dynamic Radionuclide Studies of the Cerebral Circulation.” I. Nucl. Med., 13, 658. ’Ronai, P: M., O’Reilly, R. J., Perrett, L. V. and Dmrung, T. A. R. (1973): “The Clinical Role of the Cerebral Radioangiogram: I1 Cerebrovascular Spasm in Subarachnoid Haemorrhage-A Model for Focal Occlusive Cerebrovascular Disease.” Aust. & N.Z. I . Med.. 3,530 (Abstract). *Rosenthall, L. and Martin, R. H. (1970): “Cerebral Transit of Pertechnetate Given Intravenously.” Radiology, 94, 521.
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