Clinical outcome of patients with a 'low probability' of pulmonary embolism on ventilation-perfusion lung scan.

Lung ventilation and perfusion (V/Q) scintigraphy is usually indicated when pulmonary embolism (PE) is a suspected diagnosis. Typically, V/Q scintigraphic interpretation is reported as a "normal," "low," "intermediate," or "high probability" of PE. Although a "low probability" interpretation does not exclude the diagnosis of PE, it significantly reduces the likelihood. We retrospectively analyzed up to one year of follow-up in 90 patients who were clinically suspected of having PE, but in whom V/Q scintigraphy implied a low probability of PE. None of the 90 patients demonstrated clinical evidence of PE subsequent to the V/Q scan. Our findings suggest that significant pulmonary embolism is uncommon and that the clinical course appears to be predictable in patients with a low probability V/Q scan.

Prediction of language and neurologic recovery after cerebral infarction with SPECT imaging using N-isopropyl-p-(I 123) iodoamphetamine.

Fourteen patients (10 with left-sided and 4 with right-sided cerebral infarction) were prospectively studied with single-photon emission computed tomography (SPECT) using N-isopropyl-p-(I 123) iodoamphetamine (IMP, SPECTamine) to determine its usefulness in predicting neurologic/language recovery after cerebral infarction. All neuro-SPECT imaging was performed within 30 days after infarction. Detailed assessment of neurologic and/or language recovery (after 3 months) was carried out prospectively in each patient. Patients with smaller volume IMP defects in the region of infarction demonstrated significantly better neurologic and language recovery than patients with large IMP defects. Analysis of the IMP "redistribution" phenomenon failed to demonstrate definitively a relationship with clinical recovery. It was concluded that the volume of the IMP defect can aid in predicting recovery potential after cerebral infarction.

Demonstration of focal hyperemia in acute cerebral infarction with iodine-123 iodoamphetamine.

Focal hyperemia is known to occur in regions of acute cerebral infarction. Presented here are two cases in which SPECT images with 125I-labeled iodoamphetamine demonstrated focal areas of increased tracer concentration associated with cerebral infarction. These results may have important implications regarding the physiology of iodoamphetamine in cerebral infarction and, in particular, whether the distribution of this tracer is related to regional blood flow in this setting. In addition, interpretation of iodoamphetamine images in cerebral infarction should include consideration of this finding.

The rim sign: association with acute cholecystitis.

In a retrospective analysis of 218 hepatobiliary studies in patients clinically suspected of acute cholecystitis, a rim of increased hepatic activity adjacent to the gallbladder fossa (the "rim sign") has been evaluated as a scintigraphic predictor of confirmed acute cholecystitis. Of 28 cases with pathologic confirmation of acute cholecystitis in this series, 17 (60%) demonstrated this sign. When associated with nonvisualization of the gallbladder at 1 hr, the positive predictive value of this photon-intense rim for acute cholecystitis was 94%. When the rim sign was absent, the positive predictive value of nonvisualization of the gallbladder at 1 hr for acute cholecystitis was only 36%. As this sign was always seen during the first hour postinjection, it can, when associated with nonvisualization, reduce the time required for completion of an hepatobiliary examination in suspected acute cholecystitis.

PET, CT, and MRI with Combidex for mediastinal staging in non-small cell lung carcinoma.

BACKGROUND: To determine the relative utility of positron emission tomography (PET), computed tomography (CT), and magnetic resonance imaging with Combidex (MRI-C) in the non-invasive staging of non-small cell lung cancer (NSCLC) mediastinal lymph nodes (MLN), we compared the three tests' individual performance with surgical mediastinal sampling. In contrast to prior studies, cytology was not used. METHODS: The MLN were evaluated using PET and CT in 64 NSCLC patients. MRI-C was performed in 9 of these patients. MLN with a PET standard uptake value greater than or equal to 2.5, or greater than 1 cm in the short axis by CT or lack of MRI-C signal change were considered positive for metastatic disease. All MLN were sampled and subjected to standard pathologic analysis. PET, CT, and MRI-C scans were interpreted blinded to the histopathological results. Sensitivity, specificity, and accuracy for each scan type to appropriately stage MLN was determined using pathologic results as the standard. RESULTS: Thirty patients had stage I disease, 8 stage II, 9 stage IIIA, 7 stage IIIB, and 10 stage IV. Two-hundred-and-thirty MLN were sampled. Sixteen patients had metastatic mediastinal disease. Compared to the pathological results, PET, CT, and MRI-C had a sensitivity, specificity, and accuracy of 70%, 86%, 84%; 65%, 79%, 76%; 86%, 82%, and 83%, respectively. PET and MRI-C were statistically more accurate than CT (p<0.001). In cases where PET and CT did not identify MLN involvement with NSCLC, 8% (2/25) were pathologically positive. CONCLUSIONS: PET and MRI-C are statistically more accurate than CT. However, the differences are small and may not be clinically relevant. No technique was sensitive or specific enough to change the current recommendation to perform mediastinoscopy for MLN staging in NSCLC.

Speech fluency in aphasia. Regional cerebral blood flow correlates of recovery using single-photon emission computed tomography.

This study investigated the relationship between diminished regional cerebral blood flow (rCBF) and the recovery of fluent speech in aphasia. Single-photon emission computed tomographic brain scans using [123I]N-isopropyl-p-iodoamphetamine were obtained from 14 nonfluent aphasic patients within 30 days of cerebral infarction. Measurements of speech fluency were acquired initially and at 3 months after infarction. Nearly all of the patients exhibited significant hypoperfusion to combinations of the anterior and posterior regions of the basal ganglion, the periventricular white matter, and the inferior frontal regions. Only the inferior frontal area was significantly associated with recovery of fluent speech. This region was hypoperfused in 4 of 5 patients with poor recovery while 8 of the 9 patients with good speech fluency recovery demonstrated normal rCBF to the inferior frontal region.

Heparin as a therapy for atherosclerosis: preliminary observations on the intrapulmonary administration of low-dose heparin in the morning versus evening gauged by its effect on blood variables.

Reports on clinical trials with subcutaneous and intrapulmonary administration of low-dose heparin suggest that it may be an attractive therapeutic modality for the treatment of coronary artery disease because of unprecedented reduction in mortality of treated subjects. As a preliminary to a clinical trial with low-dose intrapulmonary heparin, a pilot study was conducted on three subjects. It compares overall circadian responses of 37 blood variables following intrapulmonary administration of heparin (10,500-18,800 U) in the morning (0800 h) and in the evening (2000 h). After each of these times, blood samples, mostly at 3 h intervals for the ensuing 27 h, were analyzed for heparin, APTT, TT, functional fibrinogen, CBC, enzymes, lipids, electrolytes, and hormones. Each time series was analyzed for circadian rhythm by the least-squares fit of a 24 h cosine and circadian mesors were compared by the Bingham test of rhythm parameters. Following heparin in the evening, but not in the morning, a statistically significant increase in circulating heparin levels, as well as directional increases in APTT and TT and decreases in fibrinogen, were observed in all three subjects. Same direction changes in several other variables were also observed. It is concluded that inhalation of heparin in low-dose levels results in variable circadian effects on blood parameters measured, ranging from no changes in their levels to minimal within normal range changes, and that these effects are dependent upon the timing of dose administration. It is suggested that the timed self-administration of low-dose heparin by inhalation be seriously considered for long-term clinical trials in the treatment and prevention of atherosclerosis.

Circadian distribution of proteins in urine from healthy young men.

Urine samples were collected at 3-hr intervals over a single 24-hr period from each of seven clinically healthy men who ranged in age from 21-25 years. Urines at each collection time were subsequently pooled using 20% of each volume and serially dialyzed against ammonium-barbituric acid buffer (pH 7.35 +/- 0.02), using a cellulose membrane permeable to compounds of less than 12,000-14,000 molecular weight (mw). When the dialyzed portions were then analyzed for total proteins, the sum of proteins in eight pools amounted to 74 mg. A 1 ml aliquot of each pool, representing approximately 50 micrograms of proteins, was concentrated and reconstituted. Approximately 20 micrograms of reconstituted proteins were then subjected to polyacrylamide gel electrophoresis. The stained gel was then scanned by laser densitometry and planimetry. Each aliquot revealed eight segments as identified by Coomassie and silver staining. Their molecular weights, estimated by extrapolation from concurrently run protein standards, and their total protein amounts were: 116,000 mw (9.44 mg), 91,000 mw (3.3 mg), 68,000 mw (11.58 mg), 53,000 mw (2.58 mg), 43,000 mw (9.12 mg), 32,000 mw (7.13 mg), 24,000 mw (4.52 mg) and 20,000 mw (5.27 mg). A statistically significant rhythm (P = 0.022 from ANOVA and 0.011 from Single Cosinor) was found for the excretion of total proteins, with an acrophase in the afternoon (1537) for these diurnally-active subjects.

Detectability of simulated brain activation using dual radioisotope SPECT based on size and intensity of the focal hyperactivity.

RATIONALE AND OBJECTIVES: Simultaneous single-photon emission computed tomography (SPECT) neuroimaging with both technetium-99m (99mTc) hexamethylpropyleneamine oxime (HMPAO) and iodine-123 (123I) N-isopropyl-iodoamphetamine is a recently introduced method with potential for assessing activation phenomena in the brain. However, there is limited information on the accuracy of the technique for detecting focal cortical sites of neuroactivation. We determined, in vitro, what levels of activation could be detected as a function of the size of the activated region. METHODS: A Lucite brain phantom was filled with both 123I and 99mTc so as to simulate both a nonactivated state (123I) along with focal sites of activation (99mTc). Simulated activations ranged from 0 to 18% in volumes of 7, 14, 20, and 27 cm3. Imaging was performed with a triple-detector gamma camera using a 10% symmetric window at 140 keV and 10% asymmetric window around 159 keV. No correction was made for gamma cross-talk. To determine whether a simulated activation was "detected," the 99mTc: 123I count ratios in the activated regions were compared by t test with ratios in nonactivated regions of similar volume. Detection sensitivities also were calculated as the fraction of the activated 99mTc: 123I ratios that were greater than the mean + 2 standard deviations of the corresponding nonactivated ratios. RESULTS: All sites of simulated activations of 10% or greater were detected. The detection sensitivity was 100% (95% confidence interval, 90-100%) for the two largest chambers with simulated activations of 13-18%. Activations in the 3-6% range, in the same-sized chambers, were detected with a limited sensitivity (67% with a confidence interval of 45-84%). In the 14-cm3 chamber, simulated activations in the 13-18% range were detected with 90% sensitivity (confidence interval, 74-98%). In general, the detection sensitivity was greater for larger chambers and higher levels of simulated activation. CONCLUSION: We conclude that the dual-radioisotope technique using triple-detector SPECT systems and low-energy all-purpose (LEAP) collimators should be highly reliable for identifying focal brain activations above 13% that cover at least 14 cm3 of brain cortex. Smaller, less intense sites of activation will be detected with reduced frequency. These conclusions are based on our assessment of only the physical parameters involved in this methodology and other factors (e.g., the possibility that the relation between cerebral radiotracer concentration and regional cerebral blood flow) may affect the results obtained with patients.

Frequency of false-positive septal defects on adenosine/201T1 images in patients with left bundle branch block.

The exercise 201T1 imaging procedure in patients with left bundle branch block (LBBB) is associated with a relatively high frequency of false-positive septal perfusion defects. We therefore initiated a study designed to determine the frequency of false-positive septal defects seen with adenosine/thallium imaging. In total, 900 adenosine/thallium cases performed at our institution for assessment of coronary artery disease were reviewed. Sixty-eight patients had LBBB on resting electrocardiogram (ECG) and sucessfully completed the imaging procedure, of whom 25 had coronary angiography. Only 6 of the 68 patients demonstrated reversible septal defects on thallium imaging. Of these 6 patients, 3 underwent coronary angiography and all of them had significant (> 70%) LAD stenosis. Therefore, at most only 4% of the patients with LBBB had a false-positive reversible septal defect. Three additional patients had fixed septal defects. Of these three patients, one underwent cardiac catheterization and was found not to have significant LAD stenosis. The results from this study suggest that adenosine/thallium imaging is associated with an acceptably low frequency of false-positive septal defects and should be used as an alternative to exercise/thallium in patients with LBBB.

Crossed cerebellar diaschisis associated with balloon test occlusion of the carotid artery.

99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) single photon emission computed tomographic (SPECT) brain imaging performed in conjunction with balloon test occlusion of the carotid artery has been used to assess risk of neurologic sequelae that might follow permanent surgical ligation of the artery. The predictive value of cortical hypoperfusion during temporary carotid occlusion for adverse neurologic events has been debated in previous publications. We believe that the risk of an adverse event is greater when a reduction in cortical perfusion during balloon test occlusion is associated with crossed cerebellar diaschisis (CCD). To test our hypothesis we evaluated the results of 27 99Tcm-HMPAO SPECT brain studies obtained in association with balloon test occlusions of the carotid artery. In each case we correlated clinical outcome with the presence or absence of regional decreases in cerebral perfusion and CCD. All of the 27 patients were free of neurologic symptoms during the balloon test occlusion. Seventeen of the 27 scintigraphic studies were felt to be abnormal, showing cortical perfusion defects all on the side of the occlusion. Among these 17 patients, five demonstrated CCD. Four of these five CCD patients showed evidence for cerebral cortical ischaemia on the side of the temporary carotid occlusion either shortly after the procedure or following carotid artery sacrifice. Of the remaining 12 patients with regionally reduced cerebral perfusion and no CCD, none showed evidence for cortical ischaemia in association with balloon test occlusion, and five of these 12 patients had carotid ligation without subsequent neurologic sequelae.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril-enhanced 99Tcm-MAG3 renal scintigraphy in subjects with suspected renovascular hypertension.

This pilot study was undertaken to generate preliminary data on the accuracy of captopril-enhanced renal scintigraphy with a relatively new radiopharmaceutical, 99Tcm-mercaptoacetyltriglycine (99Tcm-MAG3) for detecting significant renal artery stenosis. Truth data was based either on arteriographic or outcome criteria (blood pressure response to therapy). Twenty-seven subjects with suspected renovascular hypertension were studied with baseline and captopril-enhanced 99Tcm-MAG3 renal scintigraphy and renal arteriography. Scan interpretations were expressed as a probability of a significant renal artery stenosis. Scan interpretations were compared with renal arteriographic results, renal vein renin levels, blood pressure values after renal artery repair, and blood pressure control after 4-26 months of clinical follow-up. Using > or = 50% luminal obstruction on arteriography as the reference standard for renal artery stenosis and a high probability scan representing a positive test, the test sensitivity and specificity were 33 and 97%, respectively (using high or indeterminate probability to represent a positive scan, the test sensitivity and specificity were 67 and 83%, respectively). The negative predictive value of a low probability scan for renal artery stenosis was 80%. However, including a measure of renovascular hypertension (blood pressure response to renal artery repair) as the reference standard, the accuracy of the scan improves, with the negative predictive value of a low probability scan for renovascular hypertension increasing to 97%. Scintigraphic results were also positively correlated with renal vein renin values in a statistically significant fashion (two-tailed Fisher exact test statistic = 6.43, P = 0.0219). Captopril-enhanced 99Tcm-MAG3 renal scintigraphy is a moderately accurate technique for detecting renal artery stenosis. More importantly, our preliminary findings suggest that the scintigraphic technique using 99Tcm-MAG3 appears to predict the blood pressure response to renal artery repair in subjects with suspected renovascular hypertension, thereby separating subjects with haemodynamically insignificant renal artery stenosis from those with renovascular hypertension.

Evaluation of various corrections to the standardized uptake value for diagnosis of pulmonary malignancy.

OBJECTIVE: Standard uptake values (SUVs) are widely used for quantifying the uptake of 18F-fluorodeoxyglucose (18F-FDG) in tumours. The objective of this study was to evaluate the accuracy of SUVs for malignancy in lung nodules/masses and to analyse the effects of tumour size, blood glucose levels and different body weight corrections on SUV. METHODS: One hundred and twenty-seven patients with suspicious lung lesions imaged with 18F-FDG positron emission tomography (PET) were studied retrospectively. Pathology results were used to establish lesion diagnosis in all cases. SUVs based on maximum pixel values were obtained by placing regions of interest around the focus of abnormal 18F-FDG uptake in the lungs. The SUVs were calculated using the following normalizations: body weight (BW), lean body weight (LBW), scaled body surface area (BSA), blood glucose level (Glu) and tumour size (Tsize). Receivers operating characteristic (ROC) curves were generated to compare the accuracy of different methods of SUV calculation. RESULTS: The areas under the ROC curves for SUV(BW), SUV(BW+Glu), SUV(LBW), SUV(LBW+Glu), SUV(BSA), SUV(BSA+Glu) and SUV(BW+Tsize) were 0.915, 0.912, 0.911, 0.912, 0.916, 0.909 and 0.864, respectively. CONCLUSION: The accuracy of SUV analysis for malignancy in lung nodules/masses is not improved by correction for blood glucose or tumour size or by normalizing for body surface area or lean body weight instead of body weight.

Enhanced uptake of 99Tcm-MDP in skeletal metastases from prostate cancer following initiation of hormone treatment: potential for increasing delivery of therapeutic agents.

Following androgen ablation therapy, skeletal metastases from prostate cancer appear in some instances to show an increase in 99Tcm-methylene diphosphonate (99Tcm-MDP) uptake. Such a phenomenon could represent a mechanism to increase delivery of bone-seeking therapeutic agents to skeletal metastatic sites. The aim of this study was to characterize more precisely the potential increase in 99Tcm-MDP in skeletal metastases from prostate cancer following initiation of hormone therapy. Baseline bone scans were performed within 1 week of onset of hormone therapy in patients with stage D2 prostate cancer followed by multiple repeat bone scans for up to 4-6 weeks. The count density within metastatic lesions was divided by the average count density from several areas of normal bone to obtain a lesion to normal bone uptake ratio (L/N) for each lesion in each scan. Altogether, 61 skeletal metastases were identified on bone scans from five subjects. Eighty-four percent (51/61) of these lesions showed an increase in 99Tcm-MDP activity relative to normal bone following initiation of hormone therapy with a mean peak increase of 39%. Thirty-nine of these 51 metastatic lesions showed maximum uptake at 3 weeks post-onset of hormone treatment. From our findings, it appears that approximately 3 weeks following initiation of hormone blockade, most skeletal metastases from prostate cancer will demonstrate significantly enhanced 99Tcm uptake relative to normal bone. Consequently, it may be possible to improve the uptake and effectiveness of therapeutic bone-seeking radiopharmaceuticals by administering these agents following hormone therapy in patients with prostate cancer metastases.

Evaluation of pulmonary perfusion in lung regions showing isolated xenon-133 ventilation washout defects.

Xenon-133 washout phase imaging is often used to help determine whether the etiology of a perfusion defect is embolic or due to pulmonary parenchymal pathology, such as chronic obstructive pulmonary disease. This study was designed to evaluate the pulmonary blood flow patterns associated with isolated defects on xenon washout images. Scintigraphic lung studies were reviewed until 100 cases with abnormal ventilation results were obtained. Ventilation abnormalities were compared with the corresponding perfusion scan results at the same anatomic site. Of the 208 individual lung regions with xenon abnormalities, 111 showed isolated washout defects (that is, with normal washin). Ninety-four of these 111 sites showed either normal perfusion or a small, nonsegmental corresponding perfusion defect. Three segmental perfusion defects were noted in association with isolated xenon retention. In each of these cases, however, the patient was felt actually to have pulmonary embolism. Thus, it is recommended that, for interpretation of scintigraphic images in the assessment of pulmonary embolism, lung pathology associated with isolated xenon retention not be considered a potential cause for large or segmental perfusion defects.

Dosimetric determination of I-131 activity in the treatment of recurrent, nontoxic, multinodular goiter.

Although surgical treatment of nontoxic multinodular goiter remains the most effective therapy, I-131 is a reasonable alternative in cases where thyroidectomy is not appropriate. Selection of I-131 activity in the management of nontoxic multinodular goiter has largely been empirical. The use of dosimetric measurements in guiding I-131 therapy in the treatment of a patient with a recurrent, nontoxic, multinodular goiter is described.

Visualization of metastatic liver disease on technetium-99m bone scintigraphy.

To determine the frequency with which liver metastases are visualized on bone scintigraphy, 425 pairs of liver and bone scans, performed within one month of each other, were reviewed. Sixty-three of the 425 liver scans showed metastases. Of these 63, five cases of carcinoma of the colon and six cases of carcinoma of the lung also visualized by Tc-99m MDP scintigraphy. This represented 46% of colon metastases and 15% of lung metastases detected on liver scan. Liver metastases from other primary tumors were not detected on bone scan, but the numbers for these tumors were small. The liver metastases which were detected on bone scan were significantly larger than those which were not. The literature was reviewed and the primary and secondary tumors of liver with uptake of Tc-99m phosphate compounds listed.

Scintigraphic assessment of perivesical urinary extravasation following renal transplantation.

Radionuclide scintigraphy is a safe and accurate means of detecting postoperative urologic complications in renal transplant recipients. Early identification of urinary leakage coupled with aggressive intervention significantly reduces the associated morbidity and mortality. Perivesical extravasate may be difficult to distinguish from adjacent or nearby bladder activity on scintiscan. Clarification of actual bladder contour and determination of its exact location within the pelvis may resolve such uncertainties. We describe imaging techniques that define the anatomic extent of the bladder and demonstrate our scintigraphic assessment of perivesical extravasation.

Evaluation of cerebral perfusion reserve using 5% CO2 and SPECT neuroperfusion imaging.

Anatomic features of carotid artery stenosis, as defined angiographically, do not necessarily correlate with the hemodynamic significance of the narrowing. The concept of regional cerebral vasodilatory (or perfusion) reserve has been advocated as a means of defining the hemodynamic compromise associated with carotid lesions. We evaluated the feasibility of using SPECT imaging with 5% CO2 using I-123 IMP (N-isopropyl iodoamphetamine) or Tc-99m HMPAO (hexamethylpropylene amineoxime) to measure cerebral perfusion reserve. Imaging was performed on six asymptomatic subjects and one patient with a history of transient ischemic attacks but no evidence of carotid artery disease. A perfusion reserve index (PRI) was defined to represent the percent increase in blood flow during 5% CO2 breathing in regions supplied by the middle cerebral artery normalized for injected dose and changes in blood pressure. Significant increases in cerebral perfusion were seen in six of the seven subjects studied while breathing the 5% CO2 (P less than 0.01). The mean of the PRI values for the seven subjects was 32%, with a range of -5% to 58%. We conclude that SPECT imaging with IMP or HMPAO can be used to quantitatively measure the cerebral perfusion response to 5% CO2.

Efficacy and safety of repeated samarium-153 lexidronam treatment in a patient with prostate cancer and metastatic bone pain.

A patient with stage D3 prostate cancer was given 11 separate doses of samarium-153 lexidronam (Sm-153 ethylenediaminetetramethylene phosphonate) of 1 mCi/kg (37 MBq/kg) in a period of 28 months for bone pain from metastases. With the first five doses, Sm-153 lexidronam clearly reduced his bone pain and improved his quality of life, as determined by pain-assessment scores and the patient's self-assessment of its effect on his ability to perform activities of daily living. With doses 6 through 11, pain at baseline was on average less, and as a result beneficial effects after treatment were not as apparent. Samarium-153 lexidronam produced transient decreases in the leukocyte and platelet counts, but these never became low enough to cause clinical concern. This case shows both the efficacy and the safety of Sm-153 lexidronam in repeated treatments for metastatic bone pain in patients with prostate cancer.