Real-time assessment of myocardial perfusion and wall motion during bicycle and treadmill exercise echocardiography: comparison with single photon emission computed tomography.

OBJECTIVES: We sought to determine the feasibility and accuracy of real-time imaging of myocardial contrast echocardiography (MCE) in detecting myocardial perfusion defects during exercise echocardiography compared with radionuclide tomography. BACKGROUND: Ultrasound imaging at a low mechanical index and frame rate (10 to 20 Hz) after intravenous injections of perfluorocarbon containing microbubbles has the potential to evaluate myocardial perfusion and wall motion (WVM) simultaneously and in real time. METHODS: One hundred consecutive patients with intermediate-to-high probability of coronary artery disease underwent treadmill (n = 50) or supine bicycle (n = 50) exercise echocardiography. Segmental perfusion with MCE and WM w ere assessed in real time before and at peak exercise using low mechanical index (0.3) and frame rates of 10 to 20 Hz after 0.3 ml bolus injections of intravenous Optison (Mallinckrodt Inc., San Diego, California). All patients had a dual isotope (rest thallium-201, stress sestamibi) study performed during the same exercise session, and 44 patients had subsequent quantitative coronary angiography. RESULTS: In the 100 patients, agreement between MCE and single photon emission computed tomography (SPECT) was 76%, while it was 88% between MCE and WM assessment. Compared with quantitative angiography, sensitivity of MCE, SPECT and WM was comparable (75%), with a specificity ranging from 81% to 100%. The combination of MCE and WM had the best balance between sensitivity and specificity (86% and 88%,respectively) with the highest accuracy (86%). CONCLUSIONS: The real-time assessment of myocardial perfusion during exercise stress echocardiography can be achieved with imaging at low mechanical index and frame rates. The combination of WM and MCE correlates well with SPECT and is a promising important addition to conventional stress echocardiography.

Outpatient treatment with (131)I-anti-B1 antibody: radiation exposure to family members.

UNLABELLED: The Nuclear Regulatory Commission (NRC) regulations that govern release of patients administered radioactive material have been revised to include dose-based criteria in addition to the conventional activity-based criteria. A licensee may now release a patient if the total effective dose equivalent to another individual from exposure to the released patient is not likely to exceed 5 mSv (500 mrem). The result of this dose-based release limit is that now many patients given therapeutic amounts of radioactive material no longer require hospitalization. This article presents measured dose data for 26 family members exposed to 22 patients treated for non-Hodgkin's lymphoma with (131)I-anti-B1 antibody after their release according to the new NRC dose-based regulations. METHODS: The patients received administered activities ranging from 0.94 to 4.77 GBq (25--129 mCi). Family members were provided with radiation monitoring devices (film badges, thermoluminescent or optically stimulated luminescent dosimeters, or electronic digital dosimeters). Radiation safety personnel instructed the family members on the proper wearing and use of the devices. Instruction was also provided on actions recommended to maintain doses to potentially exposed individuals as low as is reasonably achievable. RESULTS: Family members wore the dosimeters for 2--17 d, with the range of measured dose values extending from 0.17 to 4.09 mSv (17--409 mrem). The average dose for infinite time based on dosimeter readings was 32% of the predicted doses projected to be received by the family members using the NRC method provided in regulatory guide 8.39. CONCLUSION: Therapy with (131)I-anti-B1 antibody can be conducted on an outpatient basis using the established recommended protocol. The patients can be released immediately with confidence that doses to other individuals will be below the 5-mSv (500 mrem) limit.

Phase I/II trial of multiple dose 131Iodine-MAb LL2 (CD22) in patients with recurrent non-Hodgkin's lymphoma.

The purpose of this to evaluate in a phase I/II study the efficacy and toxicity of a multi-dose administration of 131I labeled CD22 monoclonal antibody (131I-MAb-LL2) in escalating dose cohorts administered to relapsed non-Hodgkin's lymphoma (NHL) patients. Twenty-one patients with relapsed NHL received one of four dose levels of 131-MAb-LL2 administered in a twice weekly pattern. Starting with dose level 2, the patients also received 20 mg of unlabeled LL2 prior to each radiolabeled dose administered. Previously stored autologous peripheral blood progenitors were reinfused in case of prolonged cytopenias. Patients could repeat the same treatment if they had stable disease or a response to the first therapy at 8 weeks, and had not received their peripheral blood progenitors with the first cycle. Combining all of the dose cohorts, there were 5 complete responses or complete responses (undetermined) and 2 partial responses for a total response rate of 7/21 (33%). There was no dose response effect with responses documented at all dose levels. Expected toxicities were hematopoietic, requiring stem cell re-infusion in 5 patients. Other toxicities included hypothyroidism in 3 patients, and human anti-mouse antibody formation (HAMA) in 4 patients. In conclusion, 131I-MAb-LL2, when administered in a multi-dose fashion with 20 mg unlabeled antibody pre-dosing, resulted in a response rate of 33% in heavily pre-treated NHL patients. Non-hematologic toxicities were mild and few in number. Further evaluation of this treatment is warranted and further dose escalation will be possible.

Clinical studies of families with hearing loss attributable to mutations in the connexin 26 gene (GJB2/DFNB1)

OBJECTIVE: This retrospective study describes the phenotype associated with the single most common cause of genetic hearing loss. The frequency of childhood deafness is estimated at 1/500. Half of this hearing loss is genetic and approximately 80% of genetic hearing loss is nonsyndromic and inherited in an autosomal recessive manner. Approximately 50% of childhood nonsyndromic recessive hearing loss is caused by mutations in the connexin 26 (Cx26) gene (GJB2/DFNB1), making it the most common form of autosomal recessive nonsyndromic hearing loss with a carrier rate estimated to be as high as 2.8%. One mutation, 35delG, accounts for approximately 75% to 80% of mutations at this gene. METHODS: Hearing loss was examined in 46 individuals from 24 families who were either homozygous or compound heterozygous for Cx26 mutations. A subset of these individuals were examined for vestibular function, otoacoustic emissions, auditory brainstem response, temporal bone computed tomography, electrocardiography, urinalyses, dysmorphology, and thyroid function. RESULTS: Although all persons had hearing impairment, no consistent audiologic phenotype was observed. Hearing loss varied from mild-moderate to profound, even within the group of families homozygous for the common mutation 35delG, suggesting that other factors modify the phenotypic effects of mutations in Cx26. Furthermore, the hearing loss was observed to be progressive in a number of cases. No associations with inner ear abnormality, thyroid dysfunction, heart conduction defect, urinalyses, dysmorphic features, or retinal abnormality were noted. CONCLUSION: Newborns with confirmed hearing loss should have Cx26 testing. Cx26 testing will help define a group in which approximately 60% will have profound or severe-profound hearing loss and require aggressive language intervention (many of these patients will be candidates for cochlear implants).

Prospective investigation of positron emission tomography in lung nodules.

PURPOSE: Solitary pulmonary nodules (SPNs) are commonly identified by chest radiographs and computed tomography (CT). Biopsies are often performed to evaluate the nodules further. An accurate, noninvasive diagnostic test could avoid the morbidity and costs of invasive tissue sampling. We evaluated the ability of fluorine-18 deoxyglucose positron emission tomography (FDG-PET) to discriminate between benign and malignant pulmonary nodules in a prospective, multicenter trial. METHODS: Eighty-nine patients who had newly identified indeterminate SPNs on chest radiographs and CT were evaluated with FDG-PET. PET data were analyzed semiquantitatively by calculating standardized uptake values (SUVs) as an index of FDG accumulation and also by a visual scoring method. PET results were compared with pathology results. RESULTS: Sixty SPNs were malignant and 29 were benign. Using SUV data, PET had an overall sensitivity and specificity for detection of malignant nodules of 92% and 90%. Visual analysis provided a slightly higher, but not statistically significant, sensitivity of 98% and lower specificity of 69%. For SPNs < or = 1.5 cm (34 of 89), the sensitivity and specificity of SUV and visual analysis were 80% and 95% and 100% and 74%, respectively. CONCLUSION: FDG-PET can accurately characterize indeterminate SPNs. PET imaging provides a noninvasive method to evaluate indeterminate SPNs, which can reduce the need for invasive tissue biopsy.

Likelihood of malignancy in a solitary pulmonary nodule: comparison of Bayesian analysis and results of FDG-PET scan.

OBJECTIVE: To compare the probability of cancer in a solitary pulmonary nodule using standard criteria with Bayesian analysis and result of 2-[F-18] fluoro-2-deoxy-D-glucose-positron emission tomographic (FDG-PET) scan. SETTING: A university hospital and a teaching Veteran Affairs Medical Center. METHODS: Retrospective analysis of 52 patients who had undergone both CT scan of the chest and a FDG-PET scan for evaluation of a solitary pulmonary nodule. FDG-PET scan was classified as abnormal or normal. Utilizing Bayesian analysis, the probability of cancer using "standard criteria" available in the literature, based on patient's age, history of previous malignancy, smoking history, size and edge of nodule, and presence or absence of calcification were calculated and compared to the probability of cancer based on an abnormal or normal FDG-PET scan. Histologic study of the nodules was the gold standard. RESULTS: The likelihood ratios for malignancy in a solitary pulmonary nodule with an abnormal FDG-PET scan was 7.11 (95% confidence interval [CI], 6.36 to 7.96), suggesting a high probability for malignancy, and 0.06 (95% CI, 0.05 to 0.07) when the PET scan was normal, suggesting a high probability for benign nodule. FDG-PET scan as a single test alone was more accurate than the standard criteria and standard criteria plus PET scan in correctly classifying nodules as malignant or benign. CONCLUSION: FDG-PET scan as a single test was a better predictor of malignancy in solitary pulmonary nodules than the standard criteria using Bayesian analysis. FDG-PET scan can be a useful adjunct test in the evaluation of solitary pulmonary nodules.

Indium-111-leukocyte imaging: a case of peritonitis mimicking inflammatory bowel disease.

Leukocytes labeled with 99mTc-HMPAO and 111In have been used extensively in imaging inflammatory disorders, including inflammatory bowel disease (IBD), which has the appearance of tubular bowel activity. Peritonitis is inflammation of the serosal surfaces lining the peritoneal cavity which envelopes the bowel, giving a pattern of diffuse abdominal uptake on imaging. We present a case of an elderly man with surgically and pathologically confirmed peritonitis whose preoperative leukocyte scan mimicked the findings of IBD. Our findings suggest that diffuse peritonitis can mimic IBD on an 111In-leukocyte scan.

Mediastinal lymph node staging of non-small-cell lung cancer: a prospective comparison of computed tomography and positron emission tomography.

We compared the abilities of positron emission tomography and computed tomography to detect N2 or N3 lymph node metastases (N2 or N3) in patients with lung cancer. Positron emission tomography detects increased rates of glucose uptake, characteristic of malignant cells. Patients with peripheral tumors smaller than 2 cm and a normal mediastinum were ineligible. All patients underwent computed tomography, positron emission tomography, and surgical staging. The American Thoracic Society lymph node map was used. Computed and positron emission tomographic scans were read by separate radiologists blinded to surgical staging results. Lymph nodes were "positive" by computed tomography if larger than 1.0 cm in short-axis diameter. Standardized uptake values were recorded from areas on positron emission tomography corresponding to those from which biopsy specimens were taken; if greater than 4.2, they were called "positive." Seventy-five lymph node stations (2.8 per patient) were analyzed in 27 patients. Computed tomography incorrectly staged the mediastinum as positive for metastases in three patients and as negative for metastases in three patients. Sensitivity and specificity of computed tomographic scans were 67% and 83%, respectively. Positron emission tomography correctly staged the mediastinum in all 27 patients. When analyzed by individual node station, there were four false positive and four false negative results by computed tomography (sensitivity = 60%, specificity = 93%, positive predictive value = 60%). Positron emission tomography mislabeled one node station as positive (100% sensitive, 98% specific, positive predictive value 91%). The differences were significant when the data were analyzed both for individual lymph node stations (p = 0.039) and for patients (p = 0.031) (McNemar test). Positron emission tomography and computed tomography are more accurate than computed tomography alone in detecting mediastinal lymph node metastases from non-small-cell lung cancer.

PET-FDG imaging and transthoracic needle lung aspiration biopsy in evaluation of pulmonary lesions. A comparative risk-benefit analysis.

BACKGROUND AND OBJECTIVE: Positron emission tomography (PET) utilizing 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) has been demonstrated to be highly accurate in differentiating benign from malignant pulmonary nodules. Transthoracic fine-needle aspiration biopsy (TTNA) is generally the initial procedure of choice in the evaluation of peripheral lesions suspected to be malignant. Our objective was to determine whether PET-FDG imaging, a noninvasive test, was equally efficacious as TTNA in the evaluation of lung lesions suspected to be malignant. PATIENT SELECTION: Thirty-three patients with 35 lung lesions who had undergone both PET-FDG imaging and TTNA were retrospectively selected from an ongoing prospective study of PET-FDG imaging in the evaluation of solitary pulmonary nodules. MEASUREMENTS: Diagnostic efficacy was determined by calculating sensitivity, specificity, positive and negative predictive value, and overall predictive accuracy for both PET-FDG imaging and TTNA in differentiating benign from malignant lesions. Complication rate also was documented for the two tests. RESULTS: The PET imaging correctly identified all 26 malignant lesions, including 21 lesions diagnosed by TTNA and 7 of the 9 benign lung lesions. The TTNA was positive for malignancy in 21 lung lesions and missed the diagnosis of malignancy in 5 lesions. Diagnostic sensitivity, specificity, positive and negative predictive value, and overall predictive accuracy was 100, 78, 93, 100, and 94% for PET imaging and 81, 100, 100, 64, and 86 for TTNA, respectively. Pneumothorax was documented in 16 patients (46%), and 9 patients (26%) required a chest tube. There were no complications with PET imaging. CONCLUSION: We conclude that PET imaging of the lung is as efficacious as TTNA, with less risk, and offers an alternate noninvasive option in the evaluation and management of lung lesions suspected to be malignant.

Decision logic for retreatment of asymptomatic lung cancer recurrence based on positron emission tomography findings.

PURPOSE: The purpose of the study was to determine if Positron emission tomography (PET) 2-[F-18] fluoro-2-deoxy-D-glucose (FDG) imaging could detect subclinical local lung cancer recurrence and whether retreatment of such recurrence was feasible and beneficial. METHODS AND MATERIALS: Twenty patients with biopsy proven lung cancer were studied with Positron emission tomography for the purpose of detecting subclinical lung cancer recurrence over a period of 4.25 years. All patients were treated with external radiation as part or all of their therapy. Twenty patients had baseline PET and computed tomography (CT) studies for comparison with later studies. Surviving patients had a total of 40 sequential PET scans and 35 CT scans. The follow-up interval ranged from 5 to 40 months posttreatment. The differential uptake ratio (DUR) was determined for regions of interest of increased FDG uptake. RESULTS: The median DUR value of the 20 baseline PET studies was 5.59. The DUR value of greater than 3 was empirically selected as being positive for tumor detection. On baseline studies, PET had a 100% correlation with the CT findings in regard to detection of the site of primary tumor involvement. Four of 20 patients showed areas of discordance in the mediastinal and hilar areas on initial PET and CT studies. Seven of 17 patients showed discordant posttreatment PET-CT findings. Two false positive PET studies were due to radiation pneumonitis and one to macrophage glycolysis in tumor necrosis. For detection of asymptomatic tumor recurrence, analysis of sequential PET and CT studies, biopsy results, and the patient's clinical course suggested that PET had a sensitivity of 100%, specificity of 89.3%, and accuracy of 92.5%. Computerized Tomography was found to have a sensitivity of 67%, specificity of 85%, and accuracy of 82% for detection of such early-stage recurrence. Five patients went on to have retreatment with external irradiation based upon the PET evidence. Four retreated patients had biopsies that corroborated the positive PET findings, and one patient was retreated on the basis of the qualitative appearance of the posttreatment PET study. Two of the five retreated patients remain alive without evidence of tumor to 34 months following initial therapy. CONCLUSION: Positron emission tomography scanning appears to be effective in detecting and following the progression of recurrent lung cancer. Retreatment of patients with asymptomatic recurrent tumor has resulted in absent or decreased FDG activity. Monitoring of patients with PET may provide prolonged survival in patients who otherwise would fail treatment because of local tumor recurrence.

Detection of scalene lymph node metastases from lung cancer. Positron emission tomography.

Preliminary data indicate that positron emission tomography (PET) following injection of fluorodeoxyglucose F18 (FDG) is sensitive and specific for detecting malignant cells in chest tumors and mediastinal lymph nodes. We report a case of non-small cell lung cancer metastatic to clinically normal scalene lymph nodes that was correctly staged by FDG-PET.