Positron emission tomography for the evaluation of patients with colorectal cancer.

Approximately 40% of patients treated with curative intent for colorectal carcinoma eventually recur. In about one third of these patients, the lesion is localized and potentially resectable. Typically, the recurrence is characterized by findings on diagnostic imaging studies and may be accompanied by a rise in the serum carcinoembryonic antigen (CEA) levels. In a few patients, however, the asymptomatic rise in CEA is not accompanied by diagnostic findings on computed tomography (CT). We report a case herein, of a patient with rising CEA, noted 1 year after completion of adjuvant chemotherapy for node-positive colorectal cancer. CT and laparoscopic exploration were nondiagnostic. In order to further evaluate the rise in CEA, positron emission tomography (PET) was performed. PET revealed an area of increased uptake in the right lobe of the liver. Resection of the metastatic liver lesion resulted in a subsequent drop in the CEA levels.

Myocardial blood-flow response during mental stress in patients with coronary artery disease.

Positron emission tomography was used to quantify changes in myocardial blood flow during mental stress in patients with and without coronary artery disease. Blunted augmentation of myocardial blood flow during mental stress was observed in regions without significant epicardial stenosis.

Thallium scintigraphy compared with 18F-fluorodeoxyglucose positron emission tomography for assessing myocardial viability in patients with moderate versus severe left ventricular dysfunction.

Thallium-201 reinjection imaging and positron emission tomography provide concordant information regarding myocardial viability in many patients with coronary artery disease and left ventricular (LV) dysfunction. It is unclear whether this concordance applies to patients with severe, as well as those with moderate, LV dysfunction. We studied 44 patients with chronic coronary artery disease and LV dysfunction, subgrouped on the basis of severity of dysfunction: 23 patients had moderate and 21 had severe dysfunction (ejection fractions 34 +/- 6% and 19 +/- 6%). Patients underwent exercise thallium single-photon emission computed tomography (SPECT) with 3- to 4-hour redistribution and reinjection imaging, as well as positron emission tomography (PET) imaging with 18fluorodeoxyglucose and 15O-water. Data were analyzed quantitatively in aligned transaxial PET and SPECT tomograms. A myocardial region was considered nonviable by PET if 18fluorodeoxyglucose activity was <50% of that in a normal region, associated with proportional reduction in blood flow. Similarly, regions were considered nonviable by thallium if activity was <50% of activity in normal regions on redistribution and reinjection studies. Thallium SPECT and PET data were concordant regarding viability in 98% and 93% of myocardial regions, respectively, in patients with moderate and with severe LV dysfunction. Lower concordance was observed only when regions with severe irreversible thallium perfusion defects on redistribution images were considered in both groups: 86% and 78%, respectively (p <0.01). Thus, thallium SPECT with reinjection yields information regarding regional myocardial viability that is similar to that provided by PET in patients with severe as well as moderate LV dysfunction. However, there is discordance in >20% of regions manifesting severe irreversible thallium defects in patients with severely reduced LV function.

Cerebral cortical hyperactivation in response to mental stress in patients with coronary artery disease.

The central nervous system (CNS) effects of mental stress in patients with coronary artery disease (CAD) are unexplored. The present study used positron emission tomography (PET) to measure brain correlates of mental stress induced by an arithmetic serial subtraction task in CAD and healthy subjects. Mental stress resulted in hyperactivation in CAD patients compared with healthy subjects in several brain areas including the left parietal cortex [angular gyrus/parallel sulcus (area 39)], left anterior cingulate (area 32), right visual association cortex (area 18), left fusiform gyrus, and cerebellum. These same regions were activated within the CAD patient group during mental stress versus control conditions. In the group of healthy subjects, activation was significant only in the left inferior frontal gyrus during mental stress compared with counting control. Decreases in blood flow also were produced by mental stress in CAD versus healthy subjects in right thalamus (lateral dorsal, lateral posterior), right superior frontal gyrus (areas 32, 24, and 10), and right middle temporal gyrus (area 21) (in the region of the auditory association cortex). Of particular interest, a subgroup of CAD patients that developed painless myocardial ischemia during mental stress had hyperactivation in the left hippocampus and inferior parietal lobule (area 40), left middle (area 10) and superior frontal gyrus (area 8), temporal pole, and visual association cortex (area 18), and a concomitant decrease in activation observed in the anterior cingulate bilaterally, right middle and superior frontal gyri, and right visual association cortex (area 18) compared with CAD patients without myocardial ischemia. These findings demonstrate an exaggerated cerebral cortical response and exaggerated asymmetry to mental stress in individuals with CAD.

Effect of left ventricular function on the assessment of myocardial viability by technectium-99m sestamibi and correlation with positron emission tomography in patients with healed myocardial infarcts or stable angina pectoris, or both.

The accuracy of technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) for the assessment of myocardial viability in patients with coronary artery disease and left ventricular (LV) dysfunction is not defined completely. This study determines whether the performance of Tc-99m sestamibi SPECT for viability detection differs between patients with mild-to-moderate coronary artery disease. Patients with regional and/or global LV dysfunction were separated into 2 groups on the basis of LV ejection fraction (EF) at rest: group 1 (LVEF > 25%, mean 36 +/- 6%, n = 9), and group 2 (LVEF < or = 25%, mean 17 +/- 5%, n = 11). All patients underwent semiquantitative Tc-99m sestamibi SPECT and positron emission tomography (PET) at rest with N-13 ammonia and F-18 fluorodeoxyglucose. The overall regional concordance of SPECT and PET for viability detection was 89% in group 1 and 78% in group 2 (p = 0.002). Discordance in group 2 was almost exclusively due to PET viable and/or SPECT nonviable regions. In regions with hypoperfusion at rest by PET, concordance was 78% in group 1 and only 64% in group 2 (p = 0.0015). In regions with reduced perfusion and relatively increased metabolic activity ("flow: metabolism mismatch"), Tc-99m sestamibi SPECT identified 88% of regions in group 1 as viable, but only 42% of regions in group 2 (p = 0.002). Thus, while Tc-99m sestamibi semiquantitative SPECT at rest shows a good concordance with PET for the detection of myocardial viability in patients with coronary artery disease with mild-to-moderate LV dysfunction, it may underestimate myocardial viability in patients with severe LV dysfunction, particularly in those patients with hypoperfusion at rest as assessed by PET.

Diagnosis of pedal osteomyelitis with Tc-99m HMPAO labeled leukocytes.

The diagnosis of pedal osteomyelitis is often complicated by the presence of pre-existing bony abnormalities. In this study, the utility of radiolabeled white blood cell imaging for the detection of complicated pedal osteomyelitis was evaluated. Twenty-seven men and women were prospectively enrolled and underwent plain film radiography, three-phase bone scan, and Tc-99m hexamethylpropylamine oxine white blood cell scintigraphy of their feet. The presence or absence of osteomyelitis was confirmed in all subjects by microbiologic and histopatholigic analysis of resected bone tissue. The results indicated that white blood cell imaging was more sensitive (90%) and specific (86%) for infection than either bone scan (75% sensitive, 29% specific) or plain film radiography (55% sensitive, 57% specific). This preliminary study suggests that Tc-99m hexamethylpropylamine oxine-labeled white blood cell scintigraphy is a simple, accurate test for the detection of pedal osteomyelitis.

Left ventricular diastolic function: physiology, methods of assessment, and clinical significance.

Diastole, that portion of the cardiac cycle that begins with isovolumic relaxation and ends with mitral valve closure, results in ventricular filling and involves both active (energy-dependent) and passive processes. The interactions between active processes (myocardial relaxation) that primarily influence early ventricular filling and passive processes, such as loading conditions, myocardial compliance, and valvular disease, are complex. Clinical methods to assess ventricular filling include cardiac catheterization, radionuclide angiography, and echocardiography. Any measurements of diastolic function must be made with an understanding of the determinants of ventricular filling and the limitations of the diagnostic test. Many cardiac disorders are characterized by elevated pulmonary venous pressures in the face of normal systolic ventricular function, which suggests a primary abnormality of diastolic function. Abnormalities in diastolic function have been observed in coronary artery disease, congestive heart failure (with and without systolic dysfunction), hypertrophic cardiomyopathy, hypertension, and in healthy elderly subjects. Identification of these abnormalities may be useful clinically, particularly in patients with symptoms of heart failure and normal systolic function. Data are not available to determine the optimal therapy for such patients, although evidence suggests that calcium channel blockers, beta blockers, and agents that reverse myocardial hypertrophy may be useful. This review briefly summarizes the physiology of diastole, the methods of clinical assessment of diastolic function, and the role of diastolic function in cardiovascular disease.

Improvement of the age-related impairment in left ventricular diastolic filling with verapamil in the normal human heart.

BACKGROUND: Left ventricular (LV) diastolic function declines with the normal aging process. Because these changes are related to impaired active LV relaxation as well as to structural alterations, we hypothesized that verapamil might improve LV filling in elderly normal subjects compared with young normal subjects. METHODS AND RESULTS: We studied 27 normal volunteers (between 20 and 71 years old), with normal exercise tests and echocardiograms, by radionuclide angiography before and after 3 to 4 days of oral verapamil therapy. Indexes of global LV function were derived from analysis of background-corrected time-activity curves. Subjects were recruited from three age groups: young (26 +/- 4 years, n = 10), middle-aged (46 +/- 5 years, n = 9), and elderly (66 +/- 3 years, n = 8). Baseline resting heart rate, blood pressure, peak systolic wall stress, and LV ejection fraction did not differ among groups. Baseline peak LV filling rate (expressed in fractional stroke volume per second) was reduced in the middle-aged group (5.8 +/- 1.2, P < .01) and the elderly group (4.3 +/- 1.0, P < .01) compared with the young group (7.8 +/- 1.2). With verapamil, resting heart rate, peak systolic wall stress, LV ejection fraction, and peak ejection rate did not change in any group. Peak filling rate increased in the middle-aged group (to 6.8 +/- 1.5 SV/s, P < .01) and the elderly group (to 5.7 +/- 1.0 SV/s, P < .01) but did not change in the young group (8.0 +/- 1.4 SV/s). Also, time to peak filling rate decreased with verapamil in the elderly group (from 185 +/- 31 to 147 +/- 15 milliseconds, P < .01). The magnitude of change in filling rate was correlated positively with age (r = .55, P < .005). CONCLUSION: Verapamil selectively enhances LV diastolic filling in middle-aged and elderly subjects, compared with young adults, without affecting systolic function. This observation supports the hypothesis that the impairment of LV filling accompanying the normal aging process is, at least in part, a reversible phenomenon.

Clinical significance of reduced regional myocardial glucose uptake in regions with normal blood flow in patients with chronic coronary artery disease.

OBJECTIVES: The objective of this study was to assess the clinical significance of reduced regional fluorine-18 (18F) fluorodeoxyglucose uptake with normal flow in patients with chronic coronary artery disease. BACKGROUND: In patients with ischemic left ventricular dysfunction, 18F-fluorodeoxyglucose uptake may be reduced in some myocardial regions despite normal flow. The significance of this finding is unclear and has not been investigated systematically. METHODS: Twenty-three patients with coronary artery disease and impaired ventricular function (mean ejection fraction [+/- 1 SD] 28 +/- 10%) underwent positron emission tomography with 18F-fluorodeoxyglucose and oxygen-15-labeled water at rest, exercise thallium-201 tomographic imaging with rest reinjection and gated magnetic resonance imaging to measure end-diastolic wall thickness and systolic wall thickening. RESULTS: Of 168 regions with normal flow (> or = 0.7 ml/g per min), 125 (74%) had normal 18F-fluorodeoxyglucose uptake (98 +/- 10%), and the remaining 43 (26%) showed moderately reduced 18F-fluorodeoxyglucose uptake (69 +/- 8%). Systolic wall thickening was absent at rest in 14% of regions with normal 18F-fluorodeoxyglucose uptake compared with 32% of regions with reduced 18F-fluorodeoxyglucose uptake (p < 0.01). Reversible thallium abnormalities were observed in 45 (36%) of 125 regions with normal 18F-fluorodeoxyglucose uptake compared with 27 (63%) of 43 regions with reduced 18F-fluorodeoxyglucose uptake (p < 0.01). This difference was accounted for by a higher proportion of partially reversible defects in regions with reduced 18F-fluorodeoxyglucose uptake compared with regions with normal 18F-fluorodeoxyglucose uptake (42% vs. 18%, respectively, p < 0.01). CONCLUSIONS: Thus, regions with moderately reduced 18F-fluorodeoxyglucose uptake with normal flow occur commonly in patients with ischemic left ventricular dysfunction. The majority of these regions show impaired systolic function at rest and exercise-induced thallium abnormalities that are only partially reversible. These observations suggest that such regions represent an admixture of fibrotic and reversibly ischemic myocardium.

Myocardial viability in patients with chronic coronary artery disease. Comparison of 99mTc-sestamibi with thallium reinjection and [18F]fluorodeoxyglucose.

BACKGROUND: 99mTc-sestamibi and thallium imaging have similar accuracy when used for diagnostic purposes, but whether sestamibi provides accurate information regarding myocardial viability in patients with chronic coronary artery disease has not been established. Since there is minimal redistribution of sestamibi over time, it may overestimate nonviable myocardium in patients with left ventricular dysfunction, in whom blood flow may be reduced at rest. METHODS AND RESULTS: We studied 54 patients with chronic coronary artery disease with a mean ejection fraction of 34 +/- 14%. Patients underwent stress/redistribution/reinjection thallium tomography and, within a mean of 5 days, same-day rest/stress sestamibi imaging using the same exercise protocol and with patients achieving the same exercise duration. Of the 111 reversible thallium defects on either the redistribution or reinjection study, 40 (36%) were determined to be irreversible on the rest/stress sestamibi study, whereas only 3 of 63 irreversible thallium defects despite reinjection (5%) were classified to be reversible by sestamibi imaging. The concordance regarding reversibility of myocardial defects between thallium stress/redistribution/reinjection and same day rest/stress sestamibi studies was 75%. A subgroup of 25 patients also underwent positron emission tomography (PET) studies with 15O-labeled water and [18F]fluorodeoxyglucose (FDG) at rest after an oral glucose load. As in the overall group of 54 patients, there was concordance between thallium and sestamibi imaging regarding defect reversibility in 51 of 73 regions (70%). In the remaining 22 discordant regions (30%), 18 (82%) appeared irreversible by sestamibi imaging but were reversible by thallium imaging. Myocardial viability was confirmed in 17 of 18 regions, as evidenced by normal FDG uptake (10 regions) or FDG/blood flow mismatch (7 regions) on PET. These regions were present in 16 of the 25 patients studied (64%). We then explored methods to improve the sestamibi results. First, when the 18 discordant regions with irreversible sestamibi defects were further analyzed according to the severity of defects, 14 (78%) demonstrated only mild-to-moderate reduction in sestamibi activity (51% to 85% of normal activity), suggestive of predominantly viable myocardium, and the overall concordance between thallium and sestamibi studies increased to 93%. Second, when an additional 4-hour redistribution image was acquired in 18 patients after the injection of sestamibi at rest, 6 of 16 discordant irreversible regions (38%) on the rest/stress sestamibi study became reversible, thereby increasing the concordance between thallium and sestamibi studies to 82%. CONCLUSIONS: These data indicate that same-day rest/stress sestamibi imaging will incorrectly identify 36% of myocardial regions as being irreversibly impaired and nonviable compared with both thallium redistribution/reinjection and PET. However, the identification of reversible and viable myocardium can be greatly enhanced with sestamibi if an additional redistribution image is acquired after the rest sestamibi injection or if the severity of reduction in sestamibi activity within irreversible defects is considered.

Thallium reinjection demonstrates viable myocardium in regions with reverse redistribution.

BACKGROUND: The clinical significance and pathophysiological mechanisms of reverse redistribution on stress-redistribution thallium-201 myocardial scintigraphy in patients with chronic coronary artery disease are unclear. Recent studies have shown that thallium-201 reinjection is a useful technique for the detection of myocardial viability in chronic coronary artery disease. In this investigation we determined whether thallium reinjection distinguishes viable from nonviable myocardium in regions with reverse redistribution. METHODS AND RESULTS: We studied 39 patients with chronic stable coronary artery disease (age, 60 +/- 10 years), all of whom demonstrated reverse redistribution on standard exercise-redistribution thallium single-photon emission computed tomography (SPECT). Reverse redistribution was defined as > or = 10% decrease in relative thallium-201 activity between stress and redistribution images and included either the worsening of a perfusion defect apparent on post-stress images or the appearance of a new defect on the redistribution images. Thallium reinjection was performed immediately after the 3- to 4-hour redistribution study. Of 39 regions with reverse redistribution, 32 (82%) showed enhanced thallium-201 activity (> or = 10% increase) after reinjection. In the other 7 regions (18%), the scintigraphic defect persisted after reinjection. Abnormal Q waves were present in only 8 of 32 (25%) regions with enhanced thallium-201 uptake after reinjection compared with 5 of 7 (71%) regions not responding to reinjection (P < .05). Akinetic or dyskinetic wall motion was present in 3 of 32 (9%) regions showing enhanced uptake after reinjection, in contrast with 5 of 7 (71%) regions not responding to reinjection (P < .01). Critically stenosed or totally occluded coronary arteries supplied 24 of 29 (83%) regions with enhanced thallium-201 uptake after reinjection but only 2 of 7 (28%) regions not showing a positive response to reinjection (P < .05). Collateral circulation was detected in 23 of 29 (79%) regions with a positive thallium reinjection effect but in only 1 of the other 7 regions (P < .01). Sixteen of the 39 patients also underwent positron emission tomography using 18F-fluorodeoxyglucose (FDG) to assess glucose utilization and H2(15)O to assess regional blood flow. The 14 regions with reverse redistribution that responded to reinjection with enhanced thallium uptake all showed either normal patterns of FDG uptake and flow or an ischemic pattern with increased FDG uptake relative to flow. Reduced FDG uptake and reduced flow values were seen in the two regions not responding to thallium reinjection. CONCLUSIONS: These observations indicate that reverse redistribution in chronic coronary artery disease usually reflects viable myocardium, critically dependent upon collateral circulation.

Concordance and discordance between stress-redistribution-reinjection and rest-redistribution thallium imaging for assessing viable myocardium. Comparison with metabolic activity by positron emission tomography.

BACKGROUND: Stress thallium scintigraphy provides important diagnostic and prognostic information in patients with coronary artery disease by demonstrating regional myocardial ischemia. However, if the clinical question being addressed is whether a region is viable and not whether there is inducible ischemia, then it may be more reasonable to perform rest-redistribution imaging rather than stress-redistribution imaging followed by either reinjection or late redistribution. Therefore, we determined whether stress-redistribution-reinjection and rest-redistribution imaging provide the same information regarding myocardial viability. METHODS AND RESULTS: Both stress-redistribution-reinjection and rest-redistribution thallium single photon emission computed tomographic imaging was performed in 41 patients with chronic stable coronary artery disease, with quantitative analysis of regional thallium activity. Thallium reinjection was performed immediately after the 3- to 4-hour redistribution images were completed. Of the 155 myocardial regions with perfusion defects on the stress images, 91 (59%) were irreversible on conventional 3- to 4-hour redistribution images. When the outcomes of these irreversible regions were assessed after reinjection and compared with rest-redistribution images, there was concordance of data regarding myocardial viability (normal/reversible or irreversible) in 72 of the 91 (79%) irreversible defects. Twenty of the 41 patients also underwent positron emission tomography at rest with [18F]fluorodeoxyglucose and [15O]water. In these patients, stress-redistribution-reinjection and rest-redistribution imaging provided concordant information regarding myocardial viability in 427 (72%) of 594 myocardial regions and discordance in 167 regions. However, when irreversible thallium defects were further analyzed according to the severity of the thallium defect in these discordant regions, 149 of 167 (89%) demonstrated only mild-to-moderate reduction in thallium activity (51% to 85% of normal activity), and positron emission tomography verified 98% of these regions to be metabolically active and viable. Thus, when the severity of thallium activity was considered within irreversible thallium defects, the concordance between stress-redistribution-reinjection and rest-redistribution imaging regarding myocardial viability increased to 94%. CONCLUSIONS: These data indicate that one of two imaging modalities, either stress-redistribution-reinjection or rest-redistribution imaging, may be used for identifying viable myocardium. However, if there are no contraindications to stress testing, stress-redistribution-reinjection imaging provides a more comprehensive assessment of the extent and severity of coronary artery disease by demonstrating regional myocardial ischemia without jeopardizing information on myocardial viability.

Metabolic evidence of viable myocardium in regions with reduced wall thickness and absent wall thickening in patients with chronic ischemic left ventricular dysfunction.

Reduced end-diastolic wall thickness with absent systolic wall thickening has been reported to represent nonviable myocardium in patients with chronic coronary artery disease. To assess whether reduced regional end-diastolic wall thickness and absent wall thickening accurately identify nonviable myocardium, 25 patients with ischemic left ventricular dysfunction (ejection fraction at rest 27 +/- 10%) underwent positron emission tomography with oxygen-15-labeled water and 18fluorodeoxyglucose to assess metabolic activity and spin-echo gated nuclear magnetic resonance imaging to measure regional end-diastolic wall thickness and wall thickening. The presence of metabolic activity was defined as 18fluorodeoxyglucose uptake (corrected for partial volume) greater than 50% of that in normal regions. Of 355 myocardial regions evaluated, 266 were hypokinetic or normokinetic at rest and 89 were akinetic (that is, absent wall thickening). 18Fluorodeoxyglucose uptake was observed in 97% of the hypokinetic and normokinetic regions and in 74% of the akinetic regions. End-diastolic wall thickness was greater in akinetic regions with than in those without 18fluorodeoxyglucose uptake (11 +/- 4 vs. 7 +/- 3 mm, p less than 0.01). The highest values for sensitivity and specificity of end-diastolic wall thickness in predicting the absence of metabolic activity in akinetic regions were 74% and 79%, respectively, and corresponded to an end-diastolic threshold of 8 mm. However, the positive predictive accuracy was only 55% and did not improve for other end-diastolic wall thickness values. In all myocardial regions, there was only a weak correlation between 18fluorodeoxyglucose activity and either end-diastolic wall thickness (r = 0.17) or wall thickening (r = 0.32). Thus, metabolic activity is present in many regions with reduced end-diastolic wall thickness and absent wall thickening. These data indicate that assessment of regional anatomy and function may be inaccurate in distinguishing asynergic but viable myocardium from nonviable myocardium.

Systemic and left ventricular responses to exercise stress in asymptomatic patients with valvular aortic stenosis.

Patients with heart disease may have myocardial ischemia or left ventricular (LV) dysfunction without symptoms. The exercise responses of 14 asymptomatic patients with valvular aortic stenosis (AS) were studied using treadmill testing, thallium-201 scintigraphy and radionuclide angiography. Compared with age- and gender-matched control subjects, patients with AS demonstrated reduced exercise tolerance (10.7 +/- 2.5 vs 13.3 +/- 4.2 min; p = 0.06) and maximal oxygen consumption (26.7 +/- 6.3 vs 36.3 +/- 9.5 ml O2/min/kg; p = 0.004) associated with decreased peak systolic blood pressure response to exercise (177 +/- 18 vs 214 +/- 42 mm Hg; p less than 0.004). Ten of 14 patients developed ST-segment depression during exercise, only 3 of whom had reversible thallium defects. Patients with AS tended to have greater LV ejection fractions at rest (65 +/- 11 vs 58 +/- 7; p = 0.08) and significantly decreased early peak filling rates (4.8 +/- 1.3 vs 6.1 +/- 0.6 stroke volume/s; p = 0.003) compared with those of control subjects. During maximal supine exercise, patients with AS had less of an increase in ejection fraction (2 +/- 9 vs 15 +/- 7%; p less than 0.001) associated with a decrease in end-diastolic (-7 +/- 15 vs +5 +/- 16%; p = 0.06) and stroke (-6 +/- 17 vs +30 +/- 13%; p less than 0.001) volumes from baseline measurements.(ABSTRACT TRUNCATED AT 250 WORDS)