Quantitative analysis of the tomographic thallium-201 myocardial bullseye display: critical role of correcting for patient motion

Single photon emission computed tomography (SPECT) myocardial 201TI imaging appears to offer major improvements over planar imaging. Quantitative analysis of the 201TI images appears to offer major advantages over subjective analysis in planar imaging, but the three-dimensional data available in SPECT images requires special approaches to analysis and display. Thus the myocardial "bullseye" display was developed to summarize and analyze the three-dimensional images of the left ventricle in two dimensions. The relative 201TI distribution to each region of the left ventricle of an individual patient can be displayed as the number of s.d.s away from normal that the region falls. We found that patient motion during the 22 min required for SPECT imaging appeared to produce artifactual defects. Thus, computer programs were developed to quantitate motion between consecutive frames of a [201TI] SPECT myocardial imaging study, simulate nonreturning vertical motion in normal patients, and correct the acquired data for motion. Motion as small as 0.5-1.0 pixel (3-6 mm) in the vertical (axial) direction caused artifactual defects in the quantitative bullseye display that resulted in a false-positive rate of up to 40% for a +1.0 pixel shift. Patient motion of magnitude greater than the threshold value for artifact-production (0.5 pixel) occurred at a rate of 10%, and should be corrected before tomographic reconstruction.     

Cerebral blood flow imaging with thallium-201 diethyldithiocarbamate SPECT

Thallium-201 diethyldithiocarbamate ([201TI]DDC) was studied in humans as an agent for cerebral blood flow imaging. Brain uptake proved to be complete 90 sec after injection with no appreciable washout or redistribution for hours. Intracarotid injection suggested an almost 100% extraction during the first passage. Whole-body distribution studies demonstrated a brain uptake of 4.3% of the dose compared with 0.9% for [201TI]chloride. No differences were found in the distribution of [201TI]DDC versus [201TI]chloride in other organs. After the injection of 3 mCi 201TI, good quality single photon emission computed tomographic (SPECT) images of the brain were obtained with both a rotating gamma camera and a multidetector system. In ischemic brain disease, perfusion defects were easily demonstrated. We conclude that [201TI]DDC is a suitable radiopharmaceutical for SPECT studies of cerebral blood flow.     

Effect of errors in reangulation on planar and tomographic thallium-201 washout profile curves

Cardiac phantom studies were performed with and without a defect present to test the hypothesis that myocardial 201TI quantitative circumferential washout profile curves calculated from planar and rotating slant hole (RSH) collimator tomographic images are equally affected by errors in axial repositioning. Simulated stress images were acquired with the long axis of the phantom perpendicular to the camera surface and redistribution images were acquired to represent 50% 201TI washout with axial repositioning errors relative to the stress position ranging from 0 to 20 degrees in 5 degrees increments. There was a decrease in the 201TI washout profile curves compared to that expected (50%) in the wall tilted away from the camera surface, and a reciprocal increase in the 201TI washout profile curves in the wall tilted towards the camera surface for both imaging techniques whether a lesion was present or not. This effect became more pronounced as the error in axial repositioning was increased for both the planar (p less than 0.001) and the RSH tomographic (p less than 0.001) techniques. However, the deviation of the 201TI washout profile curves from that expected (50%) was greater for the planar imaging technique with or without a lesion (p less than 0.05 to 0.001). Thus, we conclude that 201TI quantitative circumferential washout profile curves calculated using this tomographic imaging technique are less affected by errors in axial repositioning than those calculated using an equivalent projection by standard planar imaging methods. These data emphasize the importance which must be placed on the repositioning of patients to obtain valid 201TI washout profile curves for the detection and localization of coronary artery disease.     

Thallium-201 diethyldithiocarbamate: an alternative to iodine-123 N-isopropyl-p-iodoamphetamine

The study of cerebral blood flow by single photon emission computed tomography (SPECT) requires lipophilic radiopharmaceuticals. The high cost and limited availability of N-isopropyl-p-[I-123]-iodoamphetamine ( [123I]IMP) led us to search for alternatives. Following our recent development of thallium-201 diethyldithiocarbamate ( [201TI]DDC), we have compared the brain uptake of [123I]IMP and [201TI]DDC in rabbits. The brain bound 1.14 +/- 0.28% (s.e.m.) of the dose of the injected [123I]IMP and 1.46 +/- 0.28% of the [201TI]DDC. Brain activity of [201TI]DDC remained stable from 1.5 min after injection up to at least 1 hr. The [201TI]DDC uptake was more instantaneous than that of [123I]IMP. The ratios of gray to white matter distribution were about equal: 1.41 for [123I]IMP and 1.44 for [201TI]DDC. The lungs retained 8.32% of the dose of [123I]IMP and only 0.53% of the [201TI]DDC. In brain macroautoradiography [201TI]DDC yielded images of good quality with excellent demarcation of gray and white matter, persisting for at least 45 min after injection. We conclude that [123I]IMP and [201TI]DDC are equally suitable for blood flow study of the rabbit brain. The first human tomographic results obtained in two healthy volunteers demonstrate that clinical application of SPECT [201TI]DDC may be feasible.     

Technetium 99m sestamibi in the assessment of chronic coronary artery disease.

Extensive work has already been performed with regard to both planar and single photon emission computed (SPECT) technetium 99m sestamibi studies. Before widespread application of optimized acquisition and processing methods, clinical results between 99mTc sestamibi and thallium 201 were remarkably similar. It is anticipated that as techniques for 99mTc sestamibi planar and SPECT imaging become optimized, improvements in sensitivity and specificity for detection of coronary artery disease, over those observed with 201TI, might be forthcoming. This expectation is based on the improved image quality inherent in the use of the 99mTc agent with its higher count rate and higher energy. This improvement in image quality may be a principal reason for laboratories to switch from 201TI to 99mTc sestamibi imaging. It is anticipated that, with improved imaging characteristics, it will be easier for the average community hospital to obtain higher quality planar or SPECT imaging using 99mTc sestamibi rather than 201TI. In addition to improved image quality, the characteristics of 99mTc sestamibi allow gated planar or SPECT perfusion images to be obtained. It has been suggested that stress-gated SPECT sestamibi studies may provide all the information contained in a stress-rest nongated 99mTc sestamibi study, thereby potentially increasing patient throughput, a major concern with SPECT. Throughput can also be increased by using dual-isotope approaches with rest 201TI and stress technetium sestamibi acquisitions, employing either separate or simultaneous imaging with which the entire study can be accomplished in less than 2 hours. With simultaneous dual-isotope acquisition, camera time can be reduced by 50%. Finally, 99mTc sestamibi offers the advantage of the ability to perform first-pass exercise ventricular function and SPECT myocardial perfusion studies with a single injection of tracer. Regarding the assessment of myocardial viability, results to date suggest a very high degree of concordance between 201TI and 99mTc sestamibi studies using either planar or SPECT acquisition techniques. Correlative rest studies with both tracers will be of particular interest, as will preoperative and postoperative and position emission tomography correlation studies.     

Comparison of the myocardial distributions of 201Tl and 99Tcm-MIBI on SPECT images

The distributions of 201Tl and 99Tcm-MIBI on stress images were quantitatively measured in a series of 15 patients presenting with documented coronary artery disease. Following two sequential, one-week apart, peak-exercise injections of either 74 MBq of 201Tl or 370 MBq of 99Tcm-MIBI, tomographic views of the myocardium were reconstructed and two thick, central short-axis sections were divided into nine sectors. A sector was considered as showing a defect if its relative activity was lower than 30, 40, 50 or 60% of the highest level of activity in the 18 sectors. Results demonstrate that there were more defects with 201Tl than with 99Tcm-MIBI. However, the difference disappeared if the inferior wall was not included. These results suggest that depth attenuation could be, at least partly, responsible for the higher rate of positive results observed in single photon emission computed tomography with 201Tl than with 99Tcm-MIBI.     

Myocardial perfusion and clearance of 99mTc teboroxime assessed by SPECT]

99mTc teboroxime is a new myocardial imaging agent that has characteristics of high accumulation in the heart and rapid clearance. We performed tomographic teboroxime study and compared the findings with that of 201Tl. Myocardial teboroxime clearance was calculated by dynamic single photon emission computed tomography (SPECT) using continuous repetitive rotation acquisition method. Teboroxime SPECT image was reconstructed by the three-minute data started from 4 minutes after injection. In 45 myocardial regions (15 patients), complete agreement between 201Tl and 99mTc teboroxime was obtained in 33 regions (73%), when the findings were classified as normal, ischemia and infarction. Significant delay in clearance was seen in the region of coronary stenosis (greater than or equal to 75%) compared with that in the control region (p = 0.0087 at rest, and p = 0.0385 at peak exercise by paired T test). Septum-to-lateral ratios of the clearance and myocardial initial count showed positive correlation (r = 0.743). Further clinical application of this radiopharmaceutical is expected as a new myocardial imaging agent.     

Lung thallium-201 uptake during exercise emission computed tomography

To test whether the analysis of lung uptake is worth adding to the interpretation of exercise thallium-201 (201TI) emission computed tomography (ECT), a lung/heart ratio of 201TI uptake was measured from an anterior image during ECT in 25 clinically normal (Group 1), 91 angiographically normal (Group 2), and 265 subjects with coronary artery disease (Group 3). The mean +2 s.d. of ratios in Groups 1 and 2 were the same (0.37). In Group 3, 80 subjects (30%) with increased ratios (greater than 0.37) had higher frequencies of prior infarction and multi-vessel disease, more severe left ventricular dysfunction, and 201TI defects than 185 subjects with normal ratios. Subjects with markedly increased ratios (greater than 0.45) had three-vessel disease more frequently than those with slightly or moderately increased ratios (67% versus 14% or 35%). Thus the measurement of lung/heart ratios may provide information regarding the severity of coronary artery disease and should be added to the routine interpretation of exercise ECT.     

Thymic lesions in patients with myasthenia gravis: characterization with thallium 201 scintigraphy

PURPOSE: To assess thallium 201 ((201)Tl) single photon emission computed tomography (SPECT) for evaluation of thymic lesions associated with myasthenia gravis (MG), including lymphoid follicular hyperplasia (LFH) and thymoma. MATERIALS AND METHODS: (201)Tl SPECT and computed tomography (CT) were performed preoperatively in 46 patients with MG who had undergone thymectomy. SPECT was conducted 15 (early image) and 180 (delayed image) minutes after (201)Tl injection. Results were visually assessed, and (201)Tl uptake ratios (thymic lesion count density/lung count density) were measured for quantitative analysis. Uptake was analyzed among the normal thymus, LFH, and thymoma patient groups. RESULTS: Histopathologic results indicated a normal thymus, LFH, and thymoma in 19, 16, and 11 patients, respectively. Mean uptake ratios in the normal thymus, LFH, and thymoma were 0.96 (95% CI: 0.90, 1.03), 1.14 (95% CI: 1.04, 1.25), and 1.87 (95% CI: 1.56, 2.25), respectively, on early images and 1.09 (95% CI: 1.00, 1.18), 1.65 (95% CI: 1.48, 1.85), and 2.03 (95% CI: 1.65, 2.50), respectively, on delayed images. Thymoma showed more intense (201)Tl accumulation than did the normal thymus (P <.001) and LFH (P <.001) on early images. Both thymoma (P <.001) and LFH (P <.001) displayed more intense uptake than did the normal thymus on delayed images. CONCLUSION: (201)Tl SPECT can enable differentiation between normal thymus, LFH, and thymoma in patients with MG.     

Clinical significance of reverse redistribution on resting thallium-301 imaging in patients with vasospastic angina

To evaluate the clinical significance of reverse redistribution (RR) of resting 201Tl single photon emission computed tomography (SPECT) in patients with vasospastic angina (VSA), we performed left ventriculography, coronary angiography and resting 201Tl-SPECT in 22 patients with VSA. Left ventriculography showed abnormal wall motion in 17 of 22 patients (77%) and 37 of 154 segments. Thirty-one of these 37 segments (84%) were within the area perfused by coronary arteries showing acetylcholine-induced vasospasm. On 201Tl images, abnormal findings were observed in 11 of 22 patients (50%), and among them, 7 patients (32%) had RR. Seven of 37 segments (19%) having abnormal regional wall motion had RR of 201TI, and in 6 of these 7 segments (86%), accumulation of 123I-BMIPP was found to be reduced. We conclude that repetitive brief myocardial ischemia may cause myocardial injuries in patients with VSA, and that the presence of RR of 201Tl indicates the presence of myocardial injury in these patients.     

Diffuse subendocardial ischemia in a patient with aortic valve stenosis without coronary artery disease by exercise 201Tl SPECT]

A case of aortic valve stenosis without coronary artery disease was confirmed to have diffuse subendocardial ischemia by exercise Thallium-201 myocardial single photon emission computed tomography. A 72-year-old woman, who had been diagnosed as aortic valve stenosis, was admitted because of chest pain during exercise. In cardiac catheterization findings, the patient angiographically had normal coronary arteries and no asynergy of left ventricular wall motion. The peak flow velocity in continuous wave Doppler echocardiography was about 5.0 m/sec at aortic valve level, providing a pressure drop of 100 mmHg across a stenotic valve with calculating on a modified Bernoulli equation (PG = 4V2). Thallium-201 myocardial SPECT images during exercise showed a transient "dilation and a widespread wall thinning" of left ventricle with apical perfusion defect. Simultaneous electrocardiogram showed further ST depression and the patient had chest pain. In 6 months after aortic valve replacement the patient no longer demonstrated both apical perfusion defect and "wall thinning" in postoperative thallium-201 myocardial SPECT images and also had neither ST depression nor chest pain. Thus; a transient "dilation and wall thinning" of left ventricle in this patient is suspected to be a sign of diffuse subendocardial ischemia.     

Value of linsidomin in assessing myocardial viability with thallium-201 SPECT.

Myocardial viability can be assessed with rest/24 h redistribution (201)Tl myocardial single photon emission computed tomography (SPECT). The intravenous injection of vasodilators induces an early redistribution of (201)Tl and shortens the total examination time. The aim of this study was to compare the images after injection of linsidomin with the 24 h images. We studied 51 consecutive patients (38 males, 13 females), aged 66+/-11 years, referred for assessment of myocardial viability after acute myocardial infarction. SPECT acquisition at rest (30 projections over 180 degrees, 30 s per projection) was performed 20 min after injection of (201)Tl. A second acquisition (same parameters) was performed 2 min after intravenous injection of linsidomin (2 mg). A delayed acquisition was performed on the following day (50 s per step). Myocardial perfusion at rest was normal in 111 of 255 segments. For the 144 other segments, 24 h images were similar to the images acquired after the injection of linsidomin in 94% of cases (136 of 144 segments). The 24 h images showed partial redistribution that was not present after linsidomin in only eight segments (6%). Injection of linsidomin after rest acquisition can provide a reliable and more rapid assessment of myocardial viability. This very simple protocol (rest/linsidomin (201)Tl myocardial SPECT) can be performed in less than 1 h.     

Estimation of left ventricular mass in normal and infarcted canine hearts using thallium-201 SPECT

A new automated edge detection program has been developed to estimate left ventricular mass from single photon emission computed tomographic (SPECT) 201Tl images and 14 dogs were studied. Six of the 14 dogs underwent imaging before and 5 hr after coronary artery occlusion with a closed-chest technique. True left ventricular mass was determined at time of killing within 1 hr of the last 201Tl study. Left ventricular mass determined by tomography correlated well with autopsy left ventricular mass (r = 0.94; p less than 0.001, s.e.e. = 5.9 g) over a range of 62-156 g. The intraobserver variation between repeated measurements of the same SPECT study yielded an r = 0.99; p less than 0.0001; s.e.e. = 2.3 g. The reproducibility of the mass determination was assessed in four animals with two studies performed 10-14 days apart. The estimate of left ventricular mass from the two studies were highly correlated (r = 0.98; p less than 0.001) with a mean absolute difference of 4 g (3.3%). In the six dogs with a control and postinfarct study the mean total left ventricular mass by 201Tl tomography varied by less than 3.8% (r = 0.89; p less than 0.001). In conclusion, tomographic imaging with 201Tl can define left ventricular mass accurately and reproducibly in the dog model. The ability of this 201Tl tomographic left ventricular mass program to measure both normal and infarcted tissue accurately suggests the possibility of documenting interventions designed to alter left ventricular mass and of sizing acute infarcts and assessing interventions that may alter acute infarct size.     

Comparative methods for quantifying myocardial infarct size by thallium-201 SPECT

Maximum-count circumferential profile analysis of 201TI single photon emission computed tomograms (SPECT) was employed to quantify infarct size (15) in ten dogs with acute closed chest coronary occlusion (seven left anterior descending coronary artery and three left circumflex coronary artery) who underwent rest-redistribution 201TI SPECT. The extent of hypoperfused myocardium was calculated as a percentage of slice mass on rest-redistribution 201TI SPECT. Pathologic IS was determined by triphenyl tetrazolium chloride (TTC) staining. On each tomogram, SPECT IS was defined as the % of the maximum-count circumferential profile points falling below normal. To calculate total LV infarct size, slice ISs were added to one another after each was multiplied by a coefficient K that reflected the contribution of that slice to the total left ventricular mass. K was derived from an observed relationship in normal dogs between slice fractional distance from the apex and either its actual weight, its geometric SPECT area, or its count-based SPECT area, the assessment of which was independent of edge detection. Using any of these algorithms, there was a high linear correlation between the tomographic and TTC IS. A similar algorithm was also developed from tomograms of eight normal patients. These data offer promise for the clinical noninvasive assessment of the extent of hypoperfused myocardium.     

Comparison of exercise, dipyridamole, adenosine, and dobutamine stress with the use of Tc-99m tetrofosmin tomographic imaging

PURPOSE: The purpose of this study was to compare defect extent and severity and myocardial uptake with exercise and pharmacologic stress with technetium-99m (Tc-99m) tetrofosmin tomographic myocardial perfusion imaging. BACKGROUND: Detection of stress-induced myocardial perfusion defects depends on both a disparity in blood flow between normal and stenotic vessels and the extraction fraction and linearity of myocardial uptake of the tracer. There are limited clinical data for exercise or pharmacologic stress with Tc-99m tetrofosmin tomographic myocardial perfusion imaging. METHODS: Thirty-one patients with coronary artery disease and 7 with a < 5% likelihood of coronary artery disease underwent on separate days Tc-99m tetrofosmin single-photon emission computed tomographic imaging at rest and after exercise, dipyridamole, adenosine, and dobutamine stress. Images were interpreted by a blinded consensus of 3 experienced readers with a 17-segment model and 5-point scoring system. RESULTS: Compared with exercise, the summed stress score was smaller with dipyridamole (P < .01), and the reversibility score was smaller with both dipyridamole (P < .01) and dobutamine (P < .05), whereas the number of abnormal and reversible segments was less with both dipyridamole (P < .01 and P < .001, respectively) and dobutamine (both P < .05). No significant differences were found in the summed stress or reversibility scores and the number of abnormal or reversible segments between exercise and adenosine. CONCLUSIONS: Compared with exercise, defect extent, severity, and reversibility are less with dipyridamole and dobutamine with Tc-99m tetrofosmin single photon emission computed tomographic imaging.     

Optimal specificity of thallium-201 SPECT through recognition of imaging artifacts

Artifacts are produced in 201TI cardiac single photon emission computed tomography (SPECT) imaging because of a variety of causes including soft-tissue attenuation, overlying abdominal viscera, variable myocardial thickness, left bundle branch block, cardiac rotation, patient motion, and technical errors. Careful attention to quality control, utilization of motion detectors, and familiarization with potential artifacts will improve the specificity and diagnostic accuracy of 201TI SPECT for coronary artery disease.     

A patient with cardiac amyloidosis presenting a rapid increase in technetium-99m-hydroxymethylene diphosphonate accumulation

We assessed the changes in cardiac condition in a patient with cardiac amyloidosis, by means of dual nuclei single photon emission computed tomographic (SPECT) images with technetium-99m-hydroxymethylene diphosphonate (^99mTc-HMDP) and thallium-201 (²⁰¹Tl). Dual SPECT showed a marked increase in myocardial^99mTc-HMDP accumulation along with deterioration of symptoms and signs, while²⁰¹Tl scintigraphy remained almost unchanges.     

Amplitude analysis of stress technetium-99m methoxy isobutylisonitrile images in coronary artery disease.

To determine the role of rest and stress gated technetium-99m methoxyisobutylisonitrile (sestamibi), in the detection of coronary artery disease, routine Fourier analysis of these images was performed with the best septal left anterior oblique (LAO) position of 20 patients (17 men, 3 women; aged 40-75 years) who also underwent rest or redistribution/stress single photon emission tomography (SPET) (99mTc-sestamibi and Thallium-201), gated blood pool imaging and coronary angiogram. There were 6 patients with single-vessel disease, 6 with two-vessel disease, 4 with three-vessel disease, 2 with coronary spasms, 1 with a patent graft and 1 with anginal episodes but a normal angiogram result. Three normal volunteers (2 women, 1 man; aged 24-26 years) also had rest and stress gated blood pool as well as rest and stress gated 99mTc-sestamibi imaging. Rest and stress 99mTc-sestamibi amplitude and phase images depicted regional myocardial wall shortening from the outer layer of the myocardium to the center of the left ventricle as follows: a high amplitude halo of maximal negative count rate variation; a circular thinner halo of negligible amplitude; a central region of maximal positive count rate variation, as the images evolved from end-diastole to end-systole. Similar patterns with regional differences represented abnormal myocardial wall shortening. 99mTc-sestamibi and 201Tl SPET images were in agreement in 90% of the patients and 92% of myocardial regions. 201Tl SPET detected 83% of angiographically proven lesions, as compared with 80% for 99mTc-setamibi SPET and 80% for the amplitude images. The amplitude images demonstrated a larger number of other abnormalities not predicted on the angiogram, probably because they were able to detect regions with a potential for flow improvement and transient regional wall shortening abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)     

Correction for patient and organ movement in SPECT: application to exercise thallium-201 cardiac imaging

We describe a technique for correction of artifacts in exercise 201Tl single photon emission computed tomography (SPECT) images arising from abrupt or gradual translational movement of the heart during acquisition. The procedure involves the tracking of the "center of the heart" in serial projection images using an algorithm which we call "diverging squares". Each projection image is then realigned in the x-y plane so that the heart center conforms to the projected position of a fixed point in space. The shifted projections are reconstructed using the normal filtered backprojection algorithm. In validation studies, the motion correction procedure successfully eliminated movement artifacts in a heart phantom. Image quality was also improved in over one-half of 36 exercise thallium patient studies. The corrected images had smoother and more continuous left ventricular walls, greater clarity of the left ventricular cavity, and reduced streak artifacts. Rest injected or redistribution images, however, were often made worse, due to reduced heart to liver activity ratios and poor tracking of the heart center. Analysis of curves of heart position versus projection angle suggests that translation of the heart is common during imaging after exercise, and results from both abrupt patient movements, and a gradual upward shift of the heart. Our motion correction technique appears to represent a promising new approach for elimination of movement artifacts and enhancement of resolution in exercise 201Tl cardiac SPECT images.     

Gated blood-pool emission tomography: a new technique for the investigation of cardiac structure and function

ECG-gated single-photon emission-computed tomography of the intracardiac blood pool is a new technique that has not previously been widely applied. It involves the acquisition of ECG-gated images of the intracardiac blood pools labelled with sodium pertechnetate Tc 99m in 32 projections around the left-anterior hemithorax using a rotating gamma camera. From these images, tomographic sections are reconstructed orthogonal to the long axis of the left ventricle. The heart is therefore imaged three dimensionally, and more extensive information is obtained than in planar radionuclide ventriculography where imaging is usually restricted to only a single projection. Both structure and function can be studied, and the left-ventricular volume and ejection fraction, and wall motion are obtained. Of 50 patients studied, 7 cases are illustrated in order to show normal findings, examples of wall motion that were not shown by planar-contrast and radionuclide ventriculography, examples of the localisation of ventricular hypertrophy, and a comparison between blood-pool and 201TI myocardial tomography.