Calcified cerebral emboli, a "do not miss" imaging diagnosis: 22 new cases and review of the literature.

BACKGROUND AND PURPOSE: Calcified cerebral emboli are a rarely reported but devastating cause of stroke and may be the first manifestation of vascular or cardiac disease. Our aim was to evaluate the diagnosis, prevalence, imaging appearance, presumed embolic source, treatment, and outcome of patients with calcified cerebral emboli. MATERIALS AND METHODS: Our radiology information system was searched for all CT scans by using keywords "calcified," "emboli," and their permutations. The radiology information system was also searched to identify all "stroke" CT reports to calculate the prevalence of calcified cerebral emboli. We also performed a MEDLINE search to identify all published case reports. RESULTS: Twenty-two cases were identified from our database, and 48 were cases reported from the literature. The middle cerebral artery was the site of 83% of calcified emboli. Presumed sources were calcific aortic stenosis (36%), carotid atherosclerotic plaque (30%), and mitral annular calcification (11%). Spontaneous embolism occurred in 86%. Surgical treatment was performed in 34% of patients. Sixty-four percent of the patients with calcified aortic stenosis underwent aortic valve replacement. Among those with identifiable arterial disease, 53% underwent endarterectomy. Forty-one percent of patients experienced at least 1 recurrent stroke. The prevalence of calcified cerebral emboli identified on stroke CT scans at our institution was 2.7%. Seventy-three percent of cases were correctly identified. Twenty-seven percent were misdiagnosed on initial interpretation, while 9% were overlooked on preliminary interpretation. CONCLUSIONS: Calcified cerebral emboli are more common than previously assumed, are frequently overlooked or misinterpreted, affect clinical course when diagnosed, and carry substantial risk for recurrent stroke.

Calcium 45 autoradiography and dual-isotope single-photon emission CT in a canine model of cerebral ischemia and middle cerebral artery occlusion.

PURPOSE: To determine whether transient ischemia can be separated from permanent ischemia via calcium 45 autoradiography and to assess the applicability of dual isotope single-photon emission CT (SPECT) in the evaluation of cerebral blood flow. METHODS: We examined calcium influx in 12 dogs (group A) by using whole-brain calcium 45 autoradiography: Animals received 250 microCi/kg 24 hours after 30-minute (n = 6) or permanent (n = 6) middle cerebral artery (MCA) occlusion. Forty-eight hours after MCA occlusion, 5-mm coronal brain sections were fixed for either autoradiography or pathologic examination. In a separate study, 9 mongrel dogs (group B) were given 250 microCi/kg calcium 45 and a mean dose of 700 microCi/kg technetium Tc 99m hexamethylpropyleneamine oxime intravenously. A silicone plug was then injected into the internal carotid artery and angiography was performed to verify MCA occlusion. A 10th (control) animal did not undergo occlusion. In an 11th animal, placement of the plug could not be achieved and a slurry of microfibrillar collagen was injected into the carotid artery. No angiography was performed in animals 10 and 11. After occlusion, each animal was injected with a mean dose of 126 microCi/kg simultaneous acquisition for technetium 99m and 123I-iodoamphetamine. RESULTS: In group A, all animals who had permanent MCA occlusion showed infarction and increased calcium 45 uptake in infarcted territories. None of the animals who had 30-minute occlusion had either increased calcium 45 uptake or infarction at 48 hours. In group B, 7 or 10 dogs had SPECT findings that were consistent with the calcium autoradiographic marker for ischemia. One animal died during the procedure and 1 dog served as a control. CONCLUSION: Calcium 45 autoradiography allowed distinction between areas of temporary and permanent occlusion. Iodoamphetamine imaging was not consistently sensitive to that level of ischemia. Timing of calcium influx may lead to insight that could impact timing of pharmacologic or endovascular intervention.

Diagnostic overshadowing and mental retardation: a meta-analysis.

Clinicians who minimize the significance of emotional disorders in persons with mental retardation may be displaying the diagnostic overshadowing judgmental bias. A meta-analysis of the existing literature on this bias was conducted to determine its reliability, the size of its effect, and its potential clinical significance. Results show the effect to be reliable across studies; the size of the effect was small to moderate. Interpretation of the clinical significance of these results is clouded by the absence of in vivo studies. Additional concerns include insufficient attention given to clinician and situational variables moderating the presence of diagnostic overshadowing.

Detection of cerebral hypoperfusion during trial carotid occlusion with reversal following extracranial-intracranial bypass prior to permanent occlusion.

The authors describe a patient with a large intracavernous aneurysm of the right internal carotid artery and a marked decrease in focal brain blood flow induced by temporary carotid balloon occlusion. The patient subsequently underwent a superficial temporal to middle cerebral artery bypass followed by successful carotid occlusion using detachable balloons placed proximal to the aneurysm. Postoperative rCBF demonstrated normal perfusion in the region of the right internal carotid artery distribution as well as normalization of perfusion to a previous area of baseline perfusion abnormality. Cerebral brain blood flow imaging was useful in the initial evaluation as well as the management of this patient.

Diagnostic applications of simultaneously acquired dual-isotope single-photon emission CT scans.

PURPOSE: To report the development and validation of a technique of dual tracer single-photon emission CT brain imaging using technetium-99m hexamethylpropyleneamine oxime and iodine-123 iodoamphetamine agents and the application of this technique in patients with a variety of diagnoses. METHODS: Contamination between the two isotopes' energy windows was calculated by opening both energy windows while scanning a group of patients using a single isotope. To compare uniformity of I-123 down-scatter, Tc-99m studies were performed both before and after the administration of I-123 in five of 24 dual studies. The 24 patients studied with the dual-isotope technique were evaluated during acetazolamide testing, trial balloon occlusion, or embolization of an arteriovenous malformation. RESULTS: In a dual acquisition, average count contamination of an I-123 study by Tc-99m was less than 1% of the total I-123 counts, and contamination of a Tc-99m study by I-123 was approximately 12% of the total Tc-99m counts. Tc-99m studies performed both before and after the administration of I-123 demonstrated that contaminating counts do not adversely affect scan interpretation. Dual-tracer scans were completed in all 24 patients, 10 of whom showed changes after intervention. CONCLUSIONS: Dual-tracer single-photon emission CT brain scans of adequate diagnostic quality are possible using Tc-99m and I-123.

Brain blood flow SPECT in temporary balloon occlusion of carotid and intracerebral arteries.

It is important to determine preoperatively which patients can tolerate permanent occlusion of a cervical internal carotid or cerebral artery when such a procedure may be necessary to treat cerebrovascular or neoplastic lesions. Here we report our experience in combining temporary intra-arterial balloon occlusion with concomitant cerebral blood flow imaging in preoperative evaluation of such patients. Forty-two patients with a variety of cerebrovascular and neoplastic lesions underwent trial balloon occlusion of an internal carotid or intracerebral artery. Eight patients developed both neurologic symptoms as well as brain perfusion defects during trial occlusion. Nine others developed only perfusion defects. The remainder were asymptomatic and had negative scans. Brain blood flow imaging during intra-arterial balloon occlusion identified 17 patients potentially at risk for developing postsurgical ischemic deficits. Treatment alternatives to acute arterial sacrifice were developed for these patients.

Analysis of thallium-201 single-photon emission computed tomography after intravenous dipyridamole using different quantitative measures of coronary stenosis severity and receiver operator characteristic curves.

The presence of significant coronary artery disease in individual vessels was assessed using thallium-201 single-photon emission computed tomography (SPECT) after intravenous dipyridamole. Coronary angiograms were analyzed using quantitative computer-assisted techniques in 81 men patients. Eleven men with a less than 3% probability of coronary artery disease were used as a control population. Three definitions of a hemodynamically significant coronary stenosis were studied independently: (1) a greater than 50% luminal diameter narrowing; (2) an absolute cross-sectional area less than or equal to 2.0 mm2; or (3) a greater than or equal to 70% cross-sectional area obstruction. Myocardial perfusion after dipyridamole was analyzed using the quantitative (polar map) method in 213 regions from the group with known coronary anatomy and using 33 regions from the group with a low likelihood of disease. Receiver operating characteristic curves were used to define the best cut-off point for the discrimination between normal and abnormal perfusion. When related to each of the three quantitative angiographic criteria, the optimum balance between sensitivity and specificity occurred at a defect size of greater than or equal to 8% for the left anterior descending artery, greater than or equal to 4% for the circumflex artery, and greater than 0% for the right coronary artery. Using a luminal diameter narrowing of greater than 50% to define the presence of significant coronary artery disease, these corresponded to respective sensitivities and specificities of 0.82 and 0.76 for the left anterior descending artery, 0.71 and 0.71 for the circumflex artery, and 0.76 and 0.82 for the right coronary artery. Thus analysis of receiver operator characteristic curves provides a means to define abnormalities for the SPECT polar map program after dipyridamole stress. Different definitions of coronary stenosis significance as determined by quantitative angiography did not substantially alter the results of the thallium imaging data and thus suggest that these definitions are functionally similar.

Detection and staging of small cell lung carcinoma with a technetium-labeled monoclonal antibody. A comparison with standard staging methods.

Tumor-associated radiolabeled monoclonal antibodies (MoAb) can detect neoplasms in a variety of settings. The authors conducted a study comparing the ability to detect and stage small cell lung carcinoma by using a Tc-99m labeled monoclonal antibody (NR-LU-10 Fab) (NeoRx Corp, Seattle, WA) with standard staging methods. Standard staging included a physical examination, chest x-ray, a battery of radionuclide scans and/or computerized tomographic studies (head, abdomen, and bone), and bone marrow examination. A total of 22 comparisons were performed in 17 patients (five patients had reevaluations after therapy). Fifty-four (74%) of the 73 lesions defined by standard staging were detected by the radiolabeled MoAb. Seven of eight patients (88%) classified by standard staging as having "limited stage" disease on presentation were concordantly "limited stage" by radioimmunoimaging. One patient deemed "limited stage" by standard staging was correctly upstaged (bone marrow involvement) as a result of the radiolabeled MoAb. Two patients found to have extensive disease at diagnosis were characterized as "limited stage" by the MoAb, for an overall staging accuracy of 0.88. Thirteen of 19 missed lesions were smaller than 2 cm (10 were smaller than 1 cm; 3 measured 1 to 2 cm). This comparative study shows that radioimmunoimaging by Tc-99m labeled NR-LU-10 Fab antibody is capable of complementing standard staging methods used in the evaluation of small cell lung carcinoma.

Radionuclide imaging of bone marrow metastases with a Tc-99m labeled monoclonal antibody to small cell lung carcinoma.

The detection of metastatic disease confined to the bone marrow compartment has in the past been technically limited. We have identified excellent imaging of bone marrow metastases during the evaluation of a Tc-99m labeled monoclonal antibody (NR-LU-10 Fab) (NeoRx Corp., Seattle, WA). This occurred during a study to assess the monoclonal antibody's ability to detect sites of small cell cancer (primary and metastatic). The study by design compares areas seen by the monoclonal antibody scan with those found by standard staging methods in patients with small cell lung cancer. Standard staging included chest x-rays, bone scans, CT studies of the abdomen, and histologic examination of the bone marrow. Fifteen patients have been evaluated, four on two occasions, for a total of 19 monoclonal imaging studies. Metastasis to the marrow compartment was identified by the monoclonal imaging in all patients whose bone marrow biopsies were positive for small cell carcinoma, and it was primarily responsible for the eventual detection of extensive disease (marrow involvement) in one patient. Thus it appears that compartmental bone marrow imaging for metastatic disease is possible with immunoscintigraphy.

Reverse redistribution of thallium-201 detected by SPECT imaging after dipyridamole in angina pectoris.

Reverse redistribution refers to a thallium-201 perfusion defect that develops or becomes more evident on delayed imaging compared with the initial image immediately after stress. To determine the diagnostic importance of reverse redistribution after intravenous dipyridamole, thallium-201 single photon emission computed tomography and quantitative coronary arteriography were performed in 90 men with angina pectoris. Of the 250 myocardial segments analyzed, reverse redistribution was present in 17 (7%). Minimal coronary cross-sectional area in proximal vessel segments was less than or equal to 2.0 mm2 more often in regions with transient perfusion abnormalities than in regions with reverse redistribution (66 vs 29%, p less than 0.05). Compared with regions exhibiting transient perfusion abnormalities, regions with reverse redistribution had larger proximal arterial diameters (1.9 +/- 1.1 vs 1.3 +/- 1.1 mm, p less than 0.001) and cross-sectional areas (3.9 +/- 3.1 vs 2.2 +/- 2.6 mm2, p less than 0.001). Coronary artery dimensions and relative stenosis severity did not differ between those regions with normal perfusion and those with reverse redistribution. Reverse redistribution detected by thallium-201 single photon emission computed tomographic imaging after dipyridamole is uncommon, appears to occur as frequently in normal subjects as in patients undergoing coronary arteriography and does not indicate the presence of severe coronary artery disease.

Comparison of dipyridamole-Doppler echocardiography to thallium-201 imaging and quantitative coronary arteriography in the assessment of coronary artery disease.

This study was undertaken to determine whether Doppler measurements of systolic aortic and diastolic mitral blood flow velocities could reliably detect the presence of reversible myocardial perfusion defects during intravenous dipyridamole-thallium-201 imaging. In addition, the ability of dipyridamole-Doppler echocardiography to predict the presence of significant coronary artery disease (CAD) was evaluated. Baseline and post-dipyridamole Doppler studies were performed in 10 normal control subjects and 23 patients with CAD. Aortic peak velocity and acceleration increased from baseline to post-dipyridamole in normal subjects by 0.07 +/- 0.07 m/s (p = 0.016) and 2.1 +/- 2.0 m/s2 (p = 0.009), respectively. The ratio of early to late peak transmitral velocities decreased slightly in normal subjects, by 0.18 +/- 0.72 (difference not significant), whereas the ratio of early to late transmitral velocity-time integrals increased by 0.07 +/- 0.93 (difference not significant). The response of aortic velocity and acceleration to intravenous dipyridamole was not significantly different between normal subjects, patients without reversible thallium-201 perfusion defects and patients with reversible thallium-201 perfusion defects. Furthermore, only 3 of 14 subjects with reversible thallium-201 perfusion defects had abnormal (greater than 2 standard deviations from the mean) responses of aortic velocity or acceleration to intravenous dipyridamole. No patient had an abnormal response of the early to late mitral peak velocity ratio. In addition, the response of Doppler aortic and mitral indexes to intravenous dipyridamole was not able to identify the presence of significant CAD as assessed by quantitative coronary arteriography.(ABSTRACT TRUNCATED AT 250 WORDS)

A realistic dynamic cardiac phantom for evaluating radionuclide ventriculography: description and initial studies with the left ventricular chamber.

A phantom was devised to validate scintigraphically determined left ventricular ejection fractions (LVEFs) and cardiac chamber volumes in the following simulated cardiac situations: normal contraction, moderately impaired left ventricular contraction, severely impaired left ventricular contraction, mitral regurgitation, and cardiomyopathy. The phantom, assembled from anatomically realistic cardiac chambers, simulated contraction and expansion using individual chamber pumps coordinated by a microcomputer. Scintigraphic studies were performed by sequential imaging of [99mTc]pertechnetate introduced into each chamber. The images were analyzed like conventional clinical studies, using both automatic and manual techniques. Scintigraphic techniques correlated with chamber volumes that were determined by weight to yield the following regression formulae: LVEF (by automatic method 1) = 1.08 x LVEF (by weight) -5.11; LVEF (by automatic method 2) = 1.00 x LVEF (by weight) -3.15; and LVEF (by manual method) = 1.04 x LVEF (by weight) -5.08 ml (Correlation coefficients greater than 0.98). The absolute left ventricular volumes (LVVs), determined by scintigraphy, correlated well with LVVs determined by weight. These correlations were performed with separations between the center of the left ventricle and the collimator varying from 5 cm to 9 cm. The regression formulae for 5, 7, and 9 cm distances were: LVV (by counts) = 0.99 x LVV (by weight) + 0.13, LVV (by counts) = 1.04 x LVV (by weight) + 9.08, LVV (by counts) = 0.88 x LVV (by weight) + 15.25, respectively. At 9 cm, slight volumetric underestimation occurred, as predicted from the work of Fearnow et al., possibly because of oversubtraction of background. Thus, this phantom provides a useful tool for validating scintigraphic cardiac blood-pool studies simulating a wide range of clinically relevant situations.

The human locus coeruleus: computer reconstruction of cellular distribution.

Quantitative neuroanatomical techniques were developed to map the distribution of norepinephrine-containing locus coeruleus (LC) neurons in the adult human brain. These neurons reside in the dorsolateral pontine tegmentum and are identifiable by their neuromelanin pigment content. Five brains, ranging in age from 60 to 104 years, were examined. Outlines of coronal or sagittal sections containing the LC were entered into a computer along with the location of each cell, certain neuroanatomical landmarks, and cell size. Sections were aligned with specific neuroanatomical landmarks so that the computer-generated distribution of cells was representative of the in situ distribution of cells. Analysis of (1) the number of cells in sections throughout the rostrocaudal extent of the nucleus, (2) cell size, (3) 3-dimensional reconstructions of the distribution of cells within the brain stem, and (4) 2-dimensional cell-frequency maps, make it possible to quantitatively characterize the distribution of cells within this large nucleus. The total estimated number of LC cells on both sides of the brain ranged from 45,562 to 18,940 (youngest to oldest), and mean soma area ranged from 835 to 718 micron 2 (youngest to oldest). The nucleus is "tube-like" in shape, has a rostrocaudal extent of approximately 16 mm, and is bilaterally symmetrical. Two-dimensional cell-frequency maps were developed to illustrate the regional distribution of cell frequencies at any rostrocaudal/mediolateral point on the horizontal plane; the total unilateral area of the LC ranged from 32.8 to 17.2 mm2 (youngest to oldest). The techniques developed to characterize the 2- and 3-dimensional distributions of LC neurons can be used in future studies to quantitatively examine the effects of aging and disease on this and other brain nuclei.