Tc-99m RBC SPECT showing colonic bleeding in traumatic pseudoaneurysm with arteriocolonic fistula.
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Biomedical subjects
Publications and source records attributed to W J Shih.
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Tc-99m MIBI is used as a tumor imaging agent and has been proposed to measure p-glycoprotein function, which plays an important role in tumor multidrug resistance to chemotherapy. It has been reported that lung cancer and breast cancer with a high retention of Tc-99m MIBI have been more responsive to chemotherapy than tumors with low retention. Thus Tc-99m MIBI SPECT could be used as a measure of p glycoprotein function and consequently may serve as a predictor of the tumor's responsiveness to chemotherapeutic agents. Described here are two patients with lymphomas, one with non-Hodgkin's lymphoma and the other with Hodgkin's disease, who underwent Tc-99m MIBI thoracic SPECT before and after chemotherapy. The sequential studies demonstrated a reduction in tumor size and diminished tumor uptake in one patient and disappearance of tumor uptake after a course of chemotherapy in the other patient. The data suggest that elevated Tc-99m MIBI uptake in a tumor as a result of retention by p glycoprotein not only demonstrates mediastinal involvement of lymphomas but also may be used to forecast responsiveness to chemotherapy.
Thirty-one men (age range, 46-76 years; mean age, 64.8 years) with intrathoracic masses suggesting possible malignancy on the basis of chest radiography or CT underwent preoperative Tc-99m MIBI SPECT examinations. Diagnosis was confirmed on pathologic examinations of samples obtained either at thoracotomy, esophagectomy, or by biopsy. Twenty-five patients had primary lung cancer, including squamous cell carcinoma, large cell carcinoma, adenocarcinoma, and small cell carcinoma. Two patients had lymphomas with spread to the mediastinum, and three patients had extrathoracic primary cancers (one squamous cell carcinoma of esophagus, one squamous cell carcinoma originating from a head and neck tumor, and one metastatic mediastinal leiomyosarcoma). One patient with a tuberculoma had negative results of the Tc-99m MIBI examination. Tc-99m MIBI had a 86.7% sensitivity rate, a 0% false-positive rate, and a 100% positive predictive value to detect malignant intrathoracic masses. There was a 13% false-negative rate, however, suggesting that MIBI-SPECT may underdiagnose malignant lesions. SPECT findings of these 31 patients can be classified as 1) mass with increased uptake, n = 23; 2) ring-like appearance of increased uptake, n = 3; 3) mass with absent uptake, n = 4; and 4) photon-deficient mass, n = 1. Absent uptake in patients with mass lesions could be explained by necrosis of the lesion (caseation necrosis or massive tumor necrosis with or without bleeding). Most malignant intrathoracic masses are Tc-99m MIBI avid and may be detected with a high degree of sensitivity and with an excellent positive predictive value. A positive MIBI scan may help in the clinical diagnosis of malignancy. The use of Tc-99m MIBI could serve not only as a tumor imaging agent, but also may be used to determine the extent of spread and potentially the chemotherapeutic responsiveness of a tumor.
A patient with initial complaints of leg pain and difficulty walking was found to have a large right tibial metastatic tumor and poorly differentiated adenocarcinoma of the lung. Findings from total-body bone scintigraphy include a large area of increased uptake in the proximal half of the right tibia with a photon-deficient area medially, and focal areas of uptake in a right rib, in the femoral neck and the left ileum. An irregular area of increased uptake in the left lung mass was shown by thoracic bone SPECT. This is an unusual case of a tibial metastasis as the first clinical presentation of bronchogenic adenocarcinoma.
Dawson and Lagakos (1993, Biometrics 49,1022-1032) proposed a stratified test for repeated measures data that contain missing observations. They recommended stratification based on missing data patterns and considered sufficient conditions under which the size of the test is properly retained. In this paper, we point out some practical problems with these conditions and illustrate them with their CD4 count example as well as a stimulation study. We give a less stringent condition and delineate its merit. We also discuss what to do when none of the conditions are met.
Estimation of sample size in clinical trials requires knowledge of parameters that involve the treatment effect and variability, which are usually uncertain to medical researchers. The recent release within the European Union of a Note for Guidance from the Commission for Proprietary Medical Products (CPMP) highlights the importance of this issue. Most previous papers considered the case of continuous response variables that assume a normal distribution; some regarded the portion up to the interim stage as an 'internal pilot study' and required unblinding. In this paper, our concern is with the case of binary response variables, which is more difficult than the normal case since the mean and variance are not distinct parameters. We offer a design with a simple stratification strategy that enables us to verify and update the assumption of the response rates given initially in the protocol. The design provides a method to re-estimate the sample size based on interim data while preserving the trial's blinding. An illustrative numerical example and simulation results show slight effect on the type I error rate and the decision making characteristics on sample size adjustment.
A major problem in the analysis of clinical trials is missing data from patients who drop out of the study before the predetermined schedule. In this paper we consider the situation where the outcome measure is a continuous variable and the final outcome at the end of the study is the main interest. We argue that the hypothetical complete-data marginal mean averaged over the dropout patterns is not as relevant clinically as the conditional mean of the completers together with the probability of completion or dropping out of the trial. We first take the pattern-mixture modelling approach to factoring the likelihood function, then direct the analysis to the multiple testings of a composite of hypotheses that involves the probability of dropouts and the conditional mean of the completers. We review three types of closed step-down multiple-testing procedures for this application. Data from several clinical trials are used to illustrate the proposed approach.
A 61-year-old man with a slow-growing, painless mass in the area of the right knee underwent radiographic, computed tomographic (CT), arthrographic, arteriographic, and bone scintigraphic imaging studies. Scintigraphy showed an area of intense uptake in the anterolateral part of the knee; the uptake of the knee was much higher than that of the knee joints, but the area was not connected to the joint. Radiographic findings suggested an osteocartilaginous mass which was seen to contain low-density fatty tissue on the CT exam. Arthrography revealed that there was no connection of the mass to the knee joint. Arteriography showed a mildly vascularized tumor mass. Upon removal, the mass was well encapsulated, measuring 10 x 7 x 7 cm, and consisted of integrated nodules of bone, cartilage, and fat tissue. Microscopic examination confirmed lipoma with osteochondromatous metaplasia. The intense uptake in the lipoma near the bone or joint on the bone scan and multiple osteochondromatous nodules shown on CT may serve as characteristic features of the rare chondrosseous metaplasia within a lipoma.
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Kawasaki disease (mucocutaneous lymph node syndrome) is a disease of unknown aetiology that affects infants and children, with most patients having myocardial involvement. To evaluate the incidence and nature of myocardial involvement, 30 patients with Kawasaki disease underwent both dipyridamole 201Tl-chloride myocardial single photon emission tomography (SPET) and two-dimensional echocardiography (2D-Echo), which were performed within 7 days of each other. The SPET image of 15 of 30 (50%) patients showed 27 segments with myocardial perfusion abnormalities: 6 patients had one or more segments showing redistribution; 6 patients had both one or more segments of reverse redistribution and redistribution; 2 patients had reverse redistribution; and one patient had one redistribution and one fixed defect. Eight of 15 (53.3%) SPET abnormalities included reverse redistribution. Of 15 patients with positive SPET, 13 were male (age 0.3-12 years, mean = 3.55) and 2 were female (age 3-4 years, mean = 3.5). The interval between the onset of disease and SPET ranged from 1 to 594 weeks. Of the 15 patients with a negative SPET, 10 were male (age 0.4-6 years, mean = 2.08) and 5 were female (age 0.2-5 years, mean = 1.8). The interval between the onset of the disease and SPET ranged from 2 to 54 weeks. There were no significant differences in age (P = 0.10), sex (P = 0.41) or interval between the onset of disease and SPET in the patients with positive SPET and those with negative SPET (P = 0.60). With 2D-Echo, 16 (11/15 patients with positive SPET and 5/15 patients with negative SPET) of 30 (53.3%) patients had demonstrable coronary aneurysms. There was no statistical difference (P = 0.4) in the ability to detect myocardial abnormalities between SPET and 2D-Echo. Combining SPET and 2D-Echo, detectability of myocardial involvement was 66.6% (20/30). We conclude (1) that more than 50% of the patients' myocardial involvement was expressed by the myocardial perfusion status on SPET or by coronary aneurysm on 2D-Echo. Combined SPET and 2D-Echo may be of additive benefit for the detection of myocardial involvement. All 15 patients with SPET abnormalities had one or more segments of redistribution and/or reverse redistribution, indicating myocardial ischaemia and/or damaged but viable myocardium.
A 64-yr-old man with a renal mass had a preoperative 99mTc-DTPA renal flow study and renogram. An area of minimally relative increase in flow in the upper half of the right kidney was thought to reflect the high vascularity of the renal mass. A subsequent renogram showed no mass defect in the area of relatively high flow of the right kidney. The patient had a right nephrectomy. The removed kidney showed an extrarenal mass measuring 6 x 5.5 x 5 cm at the upper pole of the kidney. The mass was confirmed to be a renal cell carcinoma, clear cell type. There was no renal tissue invasion. These finding suggest an extrarenal mass pattern may be difficult to identify with a normal appearing renogram.
Brain SPECT with HMPAO or ECD has-due to its short accumulation period--a rather high time resolution of approx 60 sec. Compared to isopropyl amphetamine (I-123) and FDG-PET, shortlasting interventions may be evaluated by SPECT. Usually, a two-step approach is used, injecting one third of the dose under baseline conditions and two thirds during intervention. The first study is then subtracted from the second study, resulting in a "difference" image which allows to calculate the effect of the intervention. These interventional procedures may include drug, mechanical, and mental intervention as well as ictal, blood pressure and receptor intervention. Moreover, the difference of pCO2 after hyperventilation or hypoventilation may also be used as a stimulus. The above mentioned procedures are described in detail.
Tc-99m MIBI is taken up avidly by viable tumor tissue and does not accumulate in the necrotic carcinoma. We present a patient who underwent Tc-99m MIBI and Tc-99m HMDP thoracic SPECTs: a large area of increased MIBI uptake with central photopenia (ring appearance) in the right upper lung localizes bone imaging agent and does not localize multiple areas of intense uptake in the metastatic hilar mediastinum lymph nodes. Rapid growth of tumor cells in the lung leading to central necrosis/ischemia accounts for bone imaging agent localization in the tumor, as well as the ring-appearance of lung mass on Tc-99m MIBI imaging. These findings may reflect less viability of the lung tumor as compared with intense MIBI uptake in hilar/mediastinal lymph node uptake without bone agent localization.
Radionuclide angiogram (RNA) and aortogram may underestimate external aneurysmal diameter. Photon deficient areas are not uncommon along the abdominal aortic aneurysm (AAA) on RNA. To determine whether or not photon deficient areas along the aneurysm could represent a large thrombus, we studied radionuclide aortic angiography in thirty-eight patients during a preoperative cardiac gated study. All the patients (men, ages from 60 to 78) had CT, US, and/or aortogram for comparison. The presence of a thrombus was determined by CT, US, and/or surgical findings. Twelve of 38 (32%) patients' RNA and blood pool images showed photon deficient areas along the aneurysmal walls having a large concentric or eccentric thrombus of the AAA. A large photon deficient area could be detected along the narrowing calibre of the aorta lumen. This finding results from a large mural thrombus being interposed between the left or right bowel/mesentery activity and the activity of the aneurysms functioning patent lumen. We concluded that a photon deficient area along an inferorenal aortic aneurysm may indicate a large thrombus of either eccentric or concentric type within an AAA.
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The appearance of radiotracer in the systemic circulation to document the visualization of the brain, kidneys, and spleen after intravenous administration of Tc-99m MAA indicates right-to-left shunts because MAA particles (20-60 microns) are supposedly trapped in the pulmonary bed (less than 15 microns). Six hypoxemia patients (1 male, 5 females; age range, 12-52 years) with intrapulmonary right-to-left shunts were evaluated by Tc-99m MAA dynamic perfusion imaging and total-body scans. Tc-99m MAA total-body imaging of the six patients with intrapulmonary right-to-left shunts (3 patients with chronic liver disease/cirrhosis of the liver and 3 patients with pulmonary arteriovenous fistulae) revealed significant radiotracer uptake in extrapulmonary organs such as the brain, kidneys, and spleen; a shunt ratio, estimated by a semiquantitative method, ranged from 17.8% to 52%. All dynamic pulmonary perfusion scans showed a normal sequence of cardiopulmonary flow without intracardiac shunts. Three patients with pulmonary arteriovenous fistulae underwent a second Tc-99m MAA total-body imaging after embolization therapy (2 patients) or lobectomy (1 patient). The result in lobectomized patients were negative for uptake in extrapulmonary organs; the two patients who underwent embolization therapy demonstrated only mild improvement. As a consequence of these findings, the authors conclude that Tc-99m MAA total-body imaging can be used for the diagnosis of intrapulmonary right-to-left shunts, as well as for the evaluation of postshunt therapy.
A 61-year-old man with medullary thyroid carcinoma and local invasion of the left lobe of the thyroid had Tc-99m MIBI SPECT and Tl-201 chloride/Tc-99m pertechnetate subtraction SPECT after left lobectomy of the thyroid, using a triple-headed gamma camera. Tl-201 chloride/Tc-99m pertechnetate subtraction demonstrated a large mass with high Tl-201 uptake in the left neck. Although there was intense uptake in the tumor in the left thyroid bed on Tc-99m MIBI neck SPECT, there was also uptake in both salivary glands and the right lobe of the thyroid gland. Thus, uptake in the right lobe of the thyroid gland and the salivary glands might not be differentiated from tumor invasion or metastasis from medullary cell carcinoma. Compared with MIBI SPECT, Tl-201 chloride/Tc-99m pertechnetate subtraction SPECT shows more apparent delineation of tumor uptake and may be a preferable technique.