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To allow automated and objective reading of nuclear medicine tomography, we have developed a set of tools for clinical analysis of myocardial perfusion tomography (PERFIT) and Brain SPECT/PET (BRASS). We exploit algorithms for image registration and use three-dimensional (3D) "normal models" for individual patient comparisons to composite datasets on a "voxel-by-voxel basis" in order to automatically determine the statistically significant abnormalities. A multistage, 3D iterative inter-subject registration of patient images to normal templates is applied, including automated masking of the external activity before final fit. In separate projects, the software has been applied to the analysis of myocardial perfusion SPECT, as well as brain SPECT and PET data. Automatic reading was consistent with visual analysis; it can be applied to the whole spectrum of clinical images, and aid physicians in the daily interpretation of tomographic nuclear medicine images.

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Extra-cardiac activity on stress scans with 99Tcm sestamibi (MIBI) may influence scan interpretation. Lung uptake represents a potential sign of severe disease, whereas abdominal uptake may interfere with visualization of myocardial defects. We assessed myocardial, lung and infradiaphragmatic abdominal activity on images at 4 min (IMM) and 1 h (DEL) post-stress in 1800 consecutive studies. Potential variation among patients in organ activity was reduced with a weight-based dosing protocol. Multifactorial analysis was used to compare organ activity, and background ratios, i.e lung/heart or abdomen/heart, on stress images to (1) result of tomography, (2) peak workload, and (3) protocol (same-day versus separate-day rest/stress). Lung/heart ratios were primarily related to tomographic abnormalities, and abdomen/heart ratios to low stress workload; neither was related to protocol, and the two measurements appeared independent. Elevated lung/heart ratios (compared to angiographic normals), present on 16% and 10% of IMM and DEL images respectively, were determined primarily by increases in regional lung activity. Lung activity (normalized for dose) was higher in cases with disease than in normals (P<0.0001 as assessed by tomography, P<0.05 in the subset with correlating angiography). Increased abdominal/heart ratios derived primarily from increased abdominal activity, but were partially dependent on reciprocal decreases in myocardial activity. Elevated MIBI lung uptake ratios on abnormal scans can be attributed primarily to increased lung persistence of the radiotracer, and would thus be consistent with their use as a sign of left ventricular failure. Elevated abdominal background is associated with both higher splanchnic activity and lower myocardial activity, and is a non-specific finding related to suboptimal exercise intensity.

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Myocardial perfusion studies have been performed for 6 years using technetium-99m (99Tcm)-sestamibi (MIBI). In this study we evaluated a newer agent, 99Tcm-tetrofosmin (TF), on a trial basis for 2 weeks, and compared the results from each week to those in an adjacent week of MIBI use. The routine protocol included weight-based dosing, frequent dipyridamole use, and separate-day rest and stress wherever possible. During the first week, TF was used with 'usual' image timing, i.e. stress tomography performed 30-60 min after stress, and ancillary immediate images performed 4 min after injection. For the second week, 'early' tomography was performed 15-30 min after stress. TF scans (n = 53) were compared with MIBI scans for the adjacent weeks (n = 54) and with a historical reference series (n = 1800). Blinded analysis was made of tomographic image quality, peak myocardial counts and background activity (lung and abdomen) on immediate and delayed acquisitions and on tomographic reconstructions. The TF and MIBI test groups were similar with respect to gender, weight, stress protocol, tracer doses, imaging times and scintigraphic findings. Using analysis of variance, the tomographic quality scores were similar for the two observers, with stress>rest (P<0.0001), 'usual'>'early' (P<0.001) and MIBI>TF (P<0.05). Myocardial counts were approximately 20% higher with the MIBI test group than with TF at all times after stress (P=0.001), and were similar to the reference population. MIBI with usual timing gave more favourable stress abdominal background ratios than the other three agent/timing combinations. Satisfactory images could be obtained with TF, but no apparent advantage over MIBI could be attained with earlier post-stress imaging. Subtle advantages for MIBI over TF were suggested by comparison of the small test groups. In our local imaging context, these conclusions were reinforced by a large control series.

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UNLABELLED: On poststress images with 99mTc-sestamibi (MIBI), increased lung uptake of the radiotracer may reflect severe or multivessel coronary artery disease. METHODS: We measured pulmonary/myocardial ratios of MIBI at standardized times on immediate poststress acquisitions and on delayed tomographic acquisitions. In 1500 sequential patients referred for rest and stress myocardial tomography, ancillary planar images were obtained 4 min postinjection at peak stress with exercise, either alone (exercise, n = 674), or after intravenous dipyridamole (dipyridamole, n = 826). RESULTS: Based on 95% confidence limits in the angiographic normals, high values for immediate acquisitions were found in 17% of dipyridamole studies and 15% of exercise studies. High values for delayed acquisitions were found in 10% of dipyridamole studies and 9% of exercise studies. For both stress modes, increased values were related (p < 0.001) to ischemic perfusion defects for immediate images, to fixed defects for delayed images, and to ventricular dilation in both cases. By logistic regression analysis, body weight and history of infarction were also minor independent determinants (p < 0.01) of delayed acquisitions. In a subset of 250 cases with angiographic correlation (163 with dipyridamole; 87 with exercise), immediate lung uptake was highly correlated with ventricular dysfunction and with coronary stenoses (p < 0.0001). Relationships were similar to those in a historic control series imaged with 201TI. Values for delayed poststress images, and for corresponding rest images, showed strong relationships to ventricular dysfunction but not to stenosis severity. CONCLUSION: The relationships of immediate lung uptake to scintigraphic and angiographic disease patterns suggest its possible diagnostic use as an indicator of stress-induced ventricular decompensation.

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BACKGROUND: This paper compares two machine learning systems, an inductive decision tree (IDT) and a back-propagation neural network (ANN), in the noninvasive assessment of coronary artery disease given a set of diagnostic input attributes. A collection of 490 patient cases were accumulated from the reference of diagnostic stress myocardial scintigraphy performed in a nuclear medicine department. All cases had correlating angiography, the results of which were used to derive the target diagnoses. Input attributes included 4 baseline clinical characteristics, 4 nonimaging stress components, and 3 scintigraphic findings. METHODS: We chose 4 possible angiographic criteria for coronary artery disease and assessed the ability of each learning system to develop a diagnostic model. The 2 machine learning systems were compared on the basis of predictive performance and explanatory power. RESULTS: Cross-validation experiments showed the 2 machine learning systems to have equivalent predictive power at the same level as the clinical scan reading. For the 70% stenosis criterion, the IDT had a sensitivity of 94 +/- 3% (mean +/- 95% confidence interval) and a specificity of 59 +/- 8%, and the ANN had a sensitivity of 97 +/- 2% and a specificity of 51 +/- 13%. However the IDT system exhibited excellent explanatory power; producing simple representations of the diagnostic models which agree with previous research. CONCLUSION: In comparison with the more widely used ANNs, the IDT learning system may bring advantages to certain problems in diagnostic classification.

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OBJECTIVE: To assess the vasodilator plus exercise (VEX) test as an adjunct to myocardial perfusion imaging with respect to the accuracy of kinetics of thallium-201 (Tl-201) and other indicators of ischemia. SETTING: A nuclear medicine laboratory in which patients referred for myocardial scintigraphy are triaged to undergo the stress component with symptom-limited bicycle exercise, dipyridamole or VEX as appropriate. DESIGN: Cases having correlating scintigraphy and angiography (n = 425) were selected retrospectively. Immediate poststress and redistribution images were quantified using a circumferential profile analysis with interpolative background subtraction. For each of nine sectors on the left anterior oblique image, multivariate analyses were performed, comparing the relative uptake and net washout of Tl-201 to the exercise workload attained, use of dipyridamole, time to redistribution, gender, and the angiographic presence and severity of stenoses at five key sites. Washout values standardized according to gender, exercise level and time to redistribution, were compared with relative uptake profiles and ST depression using receiver operating curves. RESULTS: For each sector, a significant contribution to Tl-201 washout was made by the exercise level (P < 0.001) and by at least one site of stenosis (P < 0.0001), but not by use of dipyridamole (P > 0.5); female gender was associated with increased washout (P < 0.01) except for the three lateral sectors. For each stress modality, standardized washout performed better than ST depression but not as well as relative uptake profiles in detecting coronary artery disease. CONCLUSIONS: For combined pharmacological-exercise stress, quantitative uptake profiles may assist in confirming subjective scan interpretation; washout profiles, even when standardized for gender and stress level, are suboptimal for confirming defect reversibility.

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Stress myocardial perfusion scintigraphy (SMPS) may be used to amplify or supplant information available from stress electrocardiography (ECG) in directing the clinical management of patients, including the need for coronary angiography. The apparent usefulness of SMPS may depend on referral bias, the stress mode employed and the criterion for disease. We compared markers of ischaemia on quantitative planar SMPS with 201 Tl in 503 referred patients; stress was tailored to the individual patient to include exercise (n = 154), dipyridamole (n = 118) or a combination of the two (n = 231). Four angiographic criteria of increasing severity (A-D) were targeted. The fraction of the population receiving diagnostic benefit was calculated for reversible defects (RD) or lung uptake (LU) in comparison to concurrent ST depression; abnormal baseline tracings and fixed 201Tl defects were regarded as indeterminate. Decision tree induction, a computer-learning algorithm and logistic regression were also used to assess the contribution of 13 scintigraphic and other input variables. In comparison to ST depression, RD showed incremental value in 167 (33%) patients with criterion A, decreasing to 5% with criterion D; LU showed its greatest benefit (21%) with criterion D. Both scintigraphic markers were more useful with dipyrida-mole-based tests than with exercise alone. Decision trees induced at each criterion for disease showed the predominant contribution of scintigraphic results in comparison to clinical and ECG data. In conclusion, in a referred population with a frequent requirement for pharmacological stress, the clinical utility of scintigraphy can be determined by comparison of markers of ischaemia; the results will depend, however on the angiographic criterion for disease.

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Stress/injection protocols developed for myocardial perfusion imaging with 201Tl may not be optimal for 99Tcm-sestamibi (MIBI), an agent with lower myocardial extraction and higher abdominal uptake; prolongation of exercise after radiotracer injection might improve these relative drawbacks of MIBI. We compared the kinetics of MIBI and 201Tl by acquiring dynamic planar images for 5-7 min after a bolus injection (n = 180 studies) with stress performed by supine bicycle exercise alone, intravenous dipyridamole or combined stress. Routine or prolonged protocols involved continuation of exercise for 1 or 2.5 min respectively after tracer appearance in the heart. Subsequently, the perfusion images obtained were categorized as normal or showing significant defects. Myocardial uptake of MIBI, normalized for injected dose, body weight and camera sensitivity, was only 40% of that for 201Tl; there were no differences based on test mode or scan result for either perfusion tracer. During the second minute after injection, the cavity/myocardial ratios, an index of blood pool activity, were elevated with MIBI by 25% when compared with 201Tl (P < 0.001). During the third minute, cavity activity was again higher with MIBI, but only in those subjects with abnormal scans. The prolonged exercise phase did not prevent progressive accumulation in the abdomen, but did allow cavity levels to decline before termination of exercise. The prolonged protocol may ensure that myocardial uptake of MIBI is completed during peak blood flow, and therefore is recommended for stress with exercise or with dipyridamole and exercise in combination.

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UNLABELLED: In this study, three-dimensional maps of specific coronary artery territories were derived and combined with normal distribution maps as a reference for automated characterization of defects, including location and size. METHODS: One hundred sixty-eight 99mTc-sestamibi myocardial perfusion SPECT scans from normal patients and patients with single-vessel disease were selected according to angiographic data. Five separate groups were established for men and women: normal, proximal left anterior descending (PLAD), distal left anterior descending (DLAD), right coronary artery (RCA) and left circumflex (LCx). All myocardial perfusion studies were aligned and sized to the same three-dimensional orientation using a previously developed automated image registration technique. Mean and variation three-dimensional templates were constructed from stress images in each group. Normal templates were demarcated with hypoperfusion regions obtained from disease templates. The defects were detected in the individual patient's images by a region-growing algorithm which identified abnormal voxels by comparison to the corresponding voxels in the mean and variation templates. RESULTS: Defects were quantified with respect to volume, location relative to the expected hypoperfusion zones and severity index. Abnormal regions could be marked directly on tomographic slices and visualized in various orientations. Single defects greater than 2% of the myocardium positioned within demarcated perfusion territories were detected in 105/119 abnormal patients and in 3/49 normal patients. CONCLUSION: Maps of myocardial perfusion zones created from images of angiographically selected patients provide a reference for automated localization of myocardial perfusion defects. A template-based region-growing is a robust technique for volumetric quantification and localization of abnormal regions.

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Tc-99m sestamibil demonstrates considerable renal uptake followed by net urinary clearance similar to that of creatinine. The authors have previously shown that renograms could be obtained in cardiac patients by imaging during the rest injection of the perfusion agent. The present study shows correlating Tc-99m sestamibi and Tc-99m DTPA studies in hypertensive patients with a spectrum of findings, including aortic aneurysms, asymmetry due to renovascular disease, cysts, bilateral renal dysfunction, and horseshoe kidney. Tc-99m sestamibi images have persisting background activity in the liver and spleen, but show renal structure and function in adequate detail. Quantitative analysis confirms that Tc-99m sestamibi has higher renal uptake, but less excretion than Tc-99m DTPA. Review of these correlating studies suggests straightforward transfer of diagnostic expertise with standard renography to this new application.

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UNLABELLED: To optimize the interpretation of myocardial SPECT, we developed an automated method for alignment, sizing and quantification of images using three-dimensional reference templates. METHODS: Stress and rest reference templates were built using a hybrid three-dimensional image registration scheme based on principal-axes and simplex-minimization techniques. Normal patient studies were correlated to a common orientation, position and size. Aligned volumes were added to each other to create amalgamated templates. Separate templates were built for normal stress and rest SPECT 99mTc-sestamibi scans of 23 men and 15 women. The same algorithm was used to correlate abnormal test-patient studies with respective normal templates. The robustness of the fitting algorithm was evaluated by registering data with simulated defects and by repeated registrations after arbitrary misalignment of images. To quantify regional count distribution, 18 three-dimensional segments were outlined on the templates, and counts in the segment were evaluated for all test patients. RESULTS: Our technique provided accurate and reproducible alignment of the images and compensated for varying dimensions of the myocardium by adjusting scaling parameters. The algorithm successfully registered both normal and abnormal studies. The mean registration errors caused by simulated defects were 1.5 mm for position, 1.3 degrees for tilt and 5.3% for sizing (stress images), and 1.4 mm, 2.0 degrees and 3.7% (rest images); these errors were below the limits of visual assessment. CONCLUSION: Automated three-dimensional image fitting to normal templates can be used for reproducible quantification of myocardial SPECT, eliminating operator-dependence of the results.

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UNLABELLED: High abdominal background activity of 99mTc-sestamibi may interfere with the diagnosis in studies in which a coronary vasodilator is used; supplemental dynamic exercise might reduce this problem. METHODS: Clinical and angiographic determinants of subdiaphragmatic-to-myocardial activity ratios were measured on immediate poststress left anterior oblique images and on corresponding tomographic studies 1 hr after injection in 600 sestamibi studies. Similar measurements were made in 550 historic controls with planar 201Tl imaging. Patients performed symptom-limited ergometry when there were no limiting factors, dipyridamole-handgrip in which ergometry was not possible and VEX (vasodilator followed by symptom-limited ergometry) in which exercise capacity was reduced. RESULTS: Abdominal activity was higher with sestamibi than with 201Tl, in women versus men, and with dipyridamole-based tests compared to exercise alone. Compared to the dipyridamole-handgrip, 3 min of ergometry as part of VEX decreased abdominal background (p < or = 0.02) by 18% on immediate 201Tl images, by 13% on immediate sestamibi images and by 12% on 1-hr delayed sestamibi tomoacquisitions. CONCLUSIONS: Poststress abdominal background activity is influenced by similar factors with both agents. Supplemental exercise following dipyridamole reduces potentially interfering abdominal activity but perhaps not as efficiently with sestamibi as with 201Tl.

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OBJECTIVE: To relate the diagnostic finding of stress-induced pulmonary uptake of 201thallium to the severity and site of stenoses in specific coronary arteries. DESIGN: An ad hoc series of 525 referred cases had planar myocardial perfusion scintigraphy studies within four months of correlating invasive studies; patients who had previous revascularization procedures were excluded. MEASUREMENTS: Invasive studies were read by a cardiovascular radiologist with rating of stenoses as percentage luminal diameter, and grading of ventricular function from 1 (normal) to 5 (globally hypokinetic). Lung:myocardial ratios were quantitated independently on immediate poststress 201thallium myocardial perfusion images by a nuclear medicine physician. Multivariate regression equations were used to relate pulmonary uptake to stenoses in specific arteries and to the degree of ventricular dysfunction. RESULTS: Lung:myocardial ratios showed only a minor relationship to the number of subcritical (less than 90%) stenoses, but were considerably increased when severe (at least 90%) stenoses were present. Severe stenoses in the left anterior descending artery (LAD), particularly its proximal portion, provided the most dramatic increase in this index, modified by the contrast ventriculography score and to a lesser extent by additional stenoses at other sites. Regression analysis suggested a weighting of lesions in the LAD or left mainstem by a factor of at least 3 in comparison with the right coronary and left circumflex arteries. CONCLUSIONS: Stenoses in the LAD, particularly its proximal position, play a key role in the induction of increased pulmonary uptake of 201thallium on poststress scintigrams.

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UNLABELLED: The myocardial perfusion agent, 99mTc-sestamibi (MIBI), offers the potential to combine renal and myocardial imaging because of high initial renal extraction and significant renal clearance. METHODS: Dynamic renal imaging was performed during rest MIBI injections in 3 normal subjects (NS) and 91 patients referred for cardiac assessment. Ten served as normal controls, and 81 were hypertensive. Renal activity of MIBI during the first transit, uptake and excretory phases of the study was quantified. These data were compared with the normal kinetics of 99mTc-diethylenetriaminepentaacetic acid (DTPA) in concurrent studies. RESULTS: With MIBI, clear definition of the kidneys was possible on all phases in most studies; occasionally, overlap with liver or spleen provided a minor problem. Renal MIBI activity reached levels 70% greater than DTPA during first transit and remained higher throughout the study; renal/background activity ratios were also higher on the MIBI study (p < 0.001). During the excretory phase with MIBI, hepatic and splenic activity did not decline, and gut activity increased. In NS, 40% of the total activity was excreted in the urine in 1 hr; urinary MIBI clearances approximated creatinine clearance. Asymmetry in initial renal uptake was seen in 14 of 81 hypertensive patients (17%); renal cysts and aortic dilatation could also be identified. CONCLUSION: These data suggest that ancillary renography during rest injection of MIBI could be a useful addition to the cardiovascular assessment of selected patients.

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Continent reconstruction of the lower urinary tract using the appendicovesicostomy (Mitrofanoff principle) is an excellent means of managing many patients with altered bladder function, especially those with good bladder volume and low pressure. Motivated patients unable to perform urethral catheterization because of paresis or other reasons now have a method of urinary diversion free of an appliance, though additional procedures may be necessary if bladder volume is low and/or bladder pressure is high. We no longer routinely perform appendectomy during bladder substitution or bladder augmentation procedures. By removing the appendix, we may be discarding an appendage that might prove useful should future urinary reconstruction procedures be required.

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