Isolated uterine relapse in a child with acute lymphoblastic leukemia.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
M Imbriaco
Publications and source records attributed to M Imbriaco.
Interferon-gamma and monoclonal antibody 131I-labeled CC49: outcomes in patients with androgen-independent prostate cancer.
To assess the tumor targeting, safety, and efficacy of monoclonal antibody 131I-labeled CC49 in patients with androgen-independent prostate cancer, 16 patients received 75 mCi/m2 of the radiolabeled antibody after 7 days of IFN-gamma pretreatment. Sequential tumor biopsies in three patients showed a median 5-fold (range, 2-6-fold) increase in the proportion of cells staining positively for the TAG-72 antigen, whereas one showed a decrease in staining. Fourteen patients received 131I-labeled CC49, whereas 2 showed a disease-related decrease in performance status, precluding antibody treatment. The antibody localized to sites of metastatic androgen-independent prostate cancer in 86% (12 of 14; 95% confidence interval, 57-95%) of cases. Both osseous and extraosseous sites were visualized, and in six (42%) patients, more areas were visible when the radioimmunoconjugate was used than were apparent when conventional scanning techniques were used. The localization of the conjugate in the marrow cavity was usually a site not visualized by the radionuclide bone scan, in which the isotope localizes primarily to the tumor-bone interface. The dose-limiting toxicity was thrombocytopenia because five (36%) patients showed grade IV and seven (50%) showed grade III effects. In addition, six (42%) patients, four of whom were hospitalized, showed a flare in baseline pain, and four showed a decrease in pain. No patient showed a >50% decline in prostate-specific antigen, although radionuclide bone scans remained stable in four cases for a median of 4 months. The results are consistent with dosimetry estimates showing that the delivered dose to tumor was subtherapeutic and suggest that approaches that exclusively target the bone tumor interface or the marrow stroma may be unable to completely eradicate disease in the marrow cavity. For CC49, improving outcomes would require repetitive dosing, which was precluded by the rapid development of a human antimouse antibody response.
Aged↗
A new parameter for measuring metastatic bone involvement by prostate cancer: the Bone Scan Index.
In this report, we describe a method for quantitative bone scan interpretation (the Bone Scan Index or BSI) in advanced prostate cancer. The BSI estimates the fraction of the skeleton that is involved by tumor, as well as the regional distribution of the metastases in the bones. The purpose of this report is to describe the development and validation of this method in terms of reproducibility and the application of BSI for determining extent of disease and monitoring disease progression. We analyzed 263 bone scans from 90 patients being studied under four protocols at Memorial Sloan-Kettering Cancer Center for progressive, androgen-independent prostate cancer (AIPC), who had bone scans as a part of their work-up. We determined: (a) the intraobserver and interobserver variability of the BSI; (b) the comparison between a change in BSI and prostate-specific antigen (PSA); (c) the regional distribution of bony metastases in early stage D prostate cancer (<3% skeletal involvement); and (d) the rate of growth of bony metastases from prostate cancer. A cube root transformation of the percentage of involvement of the entire skeleton was used to stabilize the variance over the entire span of values (0-60% tumor involvement). The range of interobserver variability between readers was 0.2-0.5 times the cube root of the BSI (69 scans, 18 patients). Intraobserver variability was minimal when the same reader read the same scans after a 2-year interval, showing a correlation coefficient of 0.97 (reader 1) and 0.99 (reader 2), P < 0.001. There was a parallel rise in the BSI and the PSA in 24 patients (105 scans) treated for AIPC with hydrocortisone followed by suramin at PSA relapse (Pearson's moment correlation, 0.71). In a group of 27 patients with limited bone involvement by AIPC (i.e., <3% BSI), the distribution of early metastases was not random within the skeleton but was distributed in the central skeleton in a manner that matched the distribution of the normal adult bone marrow. Also, in a group of 21 patients (62 scans), the change in BSI as a function of time after diagnosis was explored graphically. The progression of bone scan changes in AIPC, from early involvement (<3%) to late involvement, was fitted to a Gompertzian equation. It showed a rapid exponential growth phase, with an estimated tumor doubling time of 43 days when the BSI was 3.3%. The change in BSI rapidly approached a more gradual slope as the percentage of skeletal involvement increased. The BSI provides a reproducible new parameter for quantitative assessment of bone involvement by AIPC. These results suggest that the BSI will be useful for stratifying patients entering treatment protocols for extent of tumor involvement of bone. Although further study is necessary, serial bone scan BSI appears capable of quantifying both the progression of bony involvement by tumor as well as the response to treatment.
Aged↗
Segmentation of lung lesion volume by adaptive positron emission tomography image thresholding.
BACKGROUND: It is common protocol in radionuclide therapies to administer a tracer dose of a radiopharmaceutical, determine its lesion uptake and biodistribution by gamma imaging, and then use this information to determine the most effective therapeutic dose. This treatment planning approach can be used to quantitate accurately the activity and volume of lesions and organs with positron emission tomography (PET). In this article, the authors focus on the specification of appropriate volumes of interest (VoI) using PET in association with computed tomography (CT). METHODS: The authors have developed an automatic image segmentation schema to determine the VoI of metastases to the lung from PET images, under conditions of variable background activity. An elliptical Jaszczak phantom containing a set of spheres with volumes ranging from 0.4 to 5.5 mL was filled with F-18 activity (2-3 microCi/mL) corresponding to activities clinically observed in lung lesions. Images were acquired with a cold background and then with variable source-to-background (S/B) ratios of: 7.4, 5.5, 3.1, and 2.8. Lesion VoI analysis was performed on 10 patients with 17 primary or metastatic lung lesions, applying the optimum threshold values derived from the phantom experiments. Initial volume estimates for lung lesions were determined from CT images. Approximate S/B ratios were obtained for the corresponding lesions on F-18-fluoro-2-deoxy-D-glucose (18FDG)-PET images. From the CT estimate of the lesion size and the PET estimate of the S/B ratio, the appropriate optimum threshold could be chosen. The threshold was applied to the PET images to obtain lesion activity and a final estimate of the lesion volume. RESULTS: Phantom data analysis showed that image segmentation converged to a fixed threshold value (from 36% to 44%) for sphere volumes larger than 4 mL, with the exact value depending on the S/B ratios. For patients, the use of optimum threshold schema demonstrated a good correlation (r = 0.999) between the initial volume from CT and the final volume derived from the 18FDG-PET scan (P < 0.02). The mean difference for those volumes was 8.4%. CONCLUSIONS: The adaptive thresholding method applied to PET scans enables the definition of tumor VoI, which hopefully leads to accurate tumor dosimetry. This method can also be applied to small lesions (<4 mL). It should enable physicians to track objectively changes in disease status that could otherwise be obscured by the uncertainties in the region-of-interest drawing, even when the scans are delineated by the same physician.
Aged↗
Thallium-201 scintigraphy for the evaluation of tumor response to preoperative chemotherapy in patients with osteosarcoma.
BACKGROUND: The degree of tumor necrosis after preoperative intravenous chemotherapy is likely to be an indicator of prognosis for patients with primary osteosarcoma. This study was undertaken to evaluate the efficacy of thallium-201 (Tl-201) scintigraphy in assessing response to chemotherapy in patients with osteosarcoma and to correlate the findings with the degree of tumor necrosis assessed histologically. METHODS: Twenty-four patients with biopsy-proven osteosarcoma underwent Tl-201 imaging before and immediately after preoperative intravenous chemotherapy. The maximum pixel counts taken over the tumor divided by those taken of a background region yielded a tumor-to-background ratio. The percentage of change in the tumor-to-background ratio before and after chemotherapy, defined as the alteration ratio, was correlated with the percentage of tumor necrosis. The percentages of tumor necrosis were classified into 4 grades: Grade 1, <50%; Grade 2, 50-89%; Grade 3, 90- 99%; Grade 4, 100%. RESULTS: Three patients with Grade 1 histologic response had an alteration ratio of 31% +/- 4 (mean +/- standard deviation). Three patients with Grade 2 response had an alteration ratio of 76% +/- 9. Nine patients with Grade 3 response had an alteration ratio of 84% +/- 11. Nine patients with Grade 4 response had an alteration ratio of 96% +/- 5. These ratios correlated well with the histologic grades (P < 0.001). CONCLUSIONS: The results of this study suggest that Tl-201 scintigraphy is a powerful tool in the evaluation of tumor response to chemotherapy in patients with osteosarcoma.
Adolescent↗
Anteromediastinal echinococcosis.
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Echinococcosis↗
Ambulatory monitoring of left ventricular function: walk and bicycle exercise in congestive heart failure.
UNLABELLED: The aim of this study was to assess changes in left ventricular (LV) function during 6-min walk test and cardiopulmonary exercise by continuous radionuclide monitoring in patients with congestive heart failure (CHF). METHODS: Seventeen patients with CHF and 10 normal subjects underwent monitoring of LV function (Vest) during 6-min walk test and during bicycle exercise with combined analysis of pulmonary gas exchange. During cardiopulmonary exercise, all parameters of LV function were measured at rest, at the anaerobic threshold (AT) and at peak oxygen uptake (peak VO2). RESULTS: In the normal subjects, during the walk test, heart rate (HR), ejection fraction (EF), end-diastolic volume (EDV), cardiac output (CO) and stroke volume (SV) significantly increased from rest to peak (all p < 0.001), while end-systolic volume (ESV) significantly decreased from rest to peak (p < 0.001). In patients with CHF, during the walk test, HR, EDV, ESV and CO significantly increased from rest to peak (p < 0.001), EF significantly decreased from rest to peak (p < 0.001) and SV did not show significant change. During cardiopulmonary exercise, normal subjects showed a significant increase in HR and CO, from rest to AT and from AT to the peak VO2 (p < 0.001). EF, EDV and SV significantly increased from rest to AT (p < 0.001), with no significant change from AT to peak VO2. ESV decreased from rest to AT (p < 0.001), showing no significant change from AT to peak VO2. In patients with CHF, HR, CO, ESV and EDV increased significantly from rest to AT (p < 0.001) and from AT to peak VO2 (p < 0.001). EF and SV did not show significant changes from rest to AT, showing a significant decrease from AT to peak VO2 (p < 0.001). CONCLUSION: Vest can be used to evaluate cardiac responses during 6-min walk test and cardiopulmonary exercise in patients with CHF. In such patients, significant impairment of LV function is already present during submaximal physical exercise becoming more evident during the anaerobic phases of bicycle exercise.
Case-Control Studies↗
Technetium-99m-MIBI versus fluorine-18-FDG in diffuse multiple myeloma.
Experience of scintigraphic detection of bone lesion and active bone marrow involvement of multiple myeloma, especially with sestamibi and FDG-PET scans is in evolution. We report a case of intense sestamibi uptake in bone marrow correlating with the extent of the disease, while FDG-PET scans showed activity only in areas of active disease progression associated with pain. Technetium-99m-sestamibi appears to indicate the extent of the disease, while [18F]FDG-PET scans show sites of active tumor proliferation and may be useful in directing local therapy such as radiation.
Aged↗
Quantitative bone metastases analysis based on image segmentation.
UNLABELLED: Preliminary evidence indicates that the fraction of bone containing metastatic lesions is a strong prognostic indicator of survival longevity for prostate and breast cancer. Our current approach to quantify metastatic bone lesions, called the Bone Scan Index, is based on an inspection of the bone scan, estimating visually the fraction of each bone involved and then summing across all bones to determine the percentage of total skeletal involvement. This approach, however, is time consuming, subjective and dependent on individual interpretation. METHODS: To overcome these problems, a semiautomated image segmentation program was developed for the quantitation of metastases from planar whole-body bone scans. The user is required to insert a seed point into each metastatic region on the image. The algorithm then connects pixels to the seed pixel in all directions until a contrast-dependent threshold is reached. The optimal threshold for cessation of the region growing is determined from phantom studies. On the images, lesion delineation and size measurements were performed by the algorithm. Each delineated lesion is associated with a bone site using pull-down menus. The program then computes the fraction of lesion involvement in each bone based on look-up-tables containing the relationship of bone mass with race, sex, height and age. These look-up-tables were obtained by multiple regression of the skeletal mass measurements in humans. The total fraction of skeletal involvement is then obtained from the individual fractional masses. For individual fractional mass, values given in International Commission on Radiation Protection Publication No. 23 were used. RESULTS: The bone metastases analysis system has been used on 11 scans from 6 patients. The correlation was high (r = 0.83) between conventional (manually drawn region-of-interest) and this analysis system. Bone metastases analysis results in consistently lower estimates of fractional involvement in bone compared with the conventional region-of-interest drawing or visual estimation method. This is due to the apparent broadening of objects at and below the limits of resolution of the gamma camera. CONCLUSION: Image segmentation reduces the delineation and quantitation time of lesions by at least two compared with manual region-of-interest drawing. The objectivity of this technique allows the detection of small variations in follow-up patient scans for which the manual region-of-interest method may fail, due to performance variability of the user. This method preserves the diagnostic skills of the nuclear medicine physician to select which bony structures contain lesions, yet combines it with an objective delineation of the lesion.
Adolescent↗
Detection of bony metastases of androgen-independent prostate cancer by PET-FDG.
Fourteen F-18 fluorodeoxyglucose (FDG) studies were carried out in 13 patients known to have bony metastases from carcinoma of the prostate. One patient was newly diagnosed. The remaining patients had various types of therapy and were considered hormonally resistant. The average age was 67. All patients had extensive bony metastases shown on the conventional Tc99m-MDP bone scans. Only about 18% of bony lesions apparent on the conventional bone scans showed corresponding increase of FDG uptake. Anatomical correlation was performed by using co-registered images of SPECT and PET in the same area. The positive FDG uptake was not related to the duration of illness, level of PSA, previous therapy, and magnitude of disease involvement. It appears that only a small percentage of bony metastases is associated with increased glycolysis. It is possible that other metabolic processes are more important than glycolysis for providing prostate cancer with a source of energy and nutrients.
Aged↗
Visualization of myocardial metastasis of carcinoid tumor by indium-111-pentetreotide.
We present a case of metastatic carcinoid tumor metastatic to the heart, presenting as ventricular arrhythmia and diagnosed by 111Inpentetreotide scintiscan despite negative endocardial biopsy. The incidence and diagnosis of carcinoid heart disease is discussed, as well as the complementary role of high-resolution anatomical images (CT, MRI) with functional images (SPECT, PET) to determine the correct diagnosis of this rare condition.
Carcinoid Heart Disease↗
Assessment of systolic wall thickening using technetium-99m methoxyisobutylisonitrile in patients with coronary artery disease: relation to thallium-201 scintigraphy with re-injection.
The results of resting planar ECG-gated technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) imaging were compared with those of thallium-201 (Tl) re-injection after exercise-redistribution scintigraphy in 20 patients (19 men, 1 woman, mean age 53 +/- 10 years) with angiographically proven coronary artery disease. Eight normal subjects (seven men, one woman, mean age 50 +/- 8 years) constituted the control group. In these subjects, only resting 99mTc-MIBI imaging was performed. The standardized percent count increase from end-diastole to end-systole was calculated as an index of wall thickening in 13 segments for each study. Regional wall thickening index (WTI) and 99mTc-MIBI uptake were significantly different (P < 0.05) among segments classified as normal, reversible defects, irreversible defects with increased tracer uptake after re-injection (Re+) or irreversible defects with unchanged tracer uptake after re-injection (Re-) on Tl imaging. Furthermore, WTI and 99mTc-MIBI uptake were significantly higher (P < 0.05) in Re- segments with moderate reduction of Tl uptake (> or = 50% of peak activity) than in Re- segments with severe reduction of Tl uptake (< 50% of peak activity). A significant relationship between WTI and the results of Tl scintigraphy was observed (rho = 0.71, P < 0.0001). The percentage of Re- segments with severe reduction of WTI was significantly higher compared to Re+ segments (64% vs 3%, P < 0.01). Furthermore, compared with moderate Re- segments, a significantly higher percentage of severe Re- segments showed a severe reduction of WTI (86% vs 48%, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Case-Control Studies↗
Optimal determination of right ventricular filling dynamics in systemic hypertension.
To determine the optimal method of normalizing peak filling rate (PFR) determinations and apply it to the assessment of right ventricular (RV) and left ventricular (LV) filling characteristics and their interactions, 41 subjects with hypertension and 40 matched normals underwent echo-Doppler and nuclear study. Conventional normalization of PFR to end-diastolic volume (EDV) yielded poor correlations between nuclear- and echo-derived PFR (RV, r = 0.34; LV, r = 0.42), whereas nuclear and echo PFR normalized to stroke volume (SV) were closely correlated (RV, r = 0.87; LV, r = 0.92). Further, use of PFR normalized to SV revealed to close relation between RV and LV filling characteristics. Multivariate analysis confirmed that, in contrast to normalization to EDV or early to late filling-velocity ratios (E/A), peak filling rate normalized to SV was independent of ejection fraction and heart rate. In addition, RV filling impairment was related to LV filling impairment, and the effects of hypertension eliminated the independent influence of age on both LV and RV filling. In conclusion, normalization of PFR to SV may be preferable to use of EDV or E/A in evaluating RV and LV filling dynamics.
Adult↗
Enhanced detection of viable myocardium by technetium-99m-MIBI imaging after nitrate administration in chronic coronary artery disease.
UNLABELLED: The aim of this study was to assess whether nitrate administration improves the imaging capabilities of 99mTc-MIBI tomography in detecting viable myocardium in coronary artery disease (CAD). METHODS: Thirty-one patients with angiographically proven CAD and chronic LV dysfunction (ejection fraction 39% +/- 9%) underwent two 99mTc-MIBI studies on separate days: one under rest conditions and the other after nitroglycerine (0.005 mg/kg per os) administration. Within 1 wk, all patients also underwent rest-redistribution 201Tl imaging. Eight patients were also studied by echocardiography before and 5 +/- 3 mo after coronary revascularization. RESULTS: On resting 99mTc-MIBI images, 302 segments had normal uptake, 183 segments had moderately reduced uptake and 197 had severely reduced uptake. Of the segments with severely reduced uptake, 54 (27%) had increased uptake after nitroglycerine and were viable on 201Tl images. Of the 143 (73%) segments with severely reduced 99mTc-MIBI uptake and no change after nitroglycerine, 81% were nonviable on 201Tl images. In the eight patients studied before and after revascularization, 87% of segments with reversible 99mTc-MIBI defects and abnormal LV function demonstrated functional recovery after revascularization, whereas 89% of segments with irreversible 99mTc-MIBI defects did not. CONCLUSION: In patients with chronic ischemic LV dysfunction, nitrate administration improved the detection of severely hypoperfused but still viable myocardium on 99mTc-MIBI images.
Coronary Circulation↗
Myocardial viability index in chronic coronary artery disease: technetium-99m-methoxy isobutyl isonitrile redistribution.
UNLABELLED: The purpose of this study was to evaluate whether an additional redistribution image after a rest 99mTc-MIBI injection enhances detection of viable myocardium and predicts functional recovery after coronary revascularization in patients with chronic coronary artery disease (CAD). METHODS: Thirty-one patients (29 men, mean age 55 +/- 10 yr) with proven CAD and left ventricular (LV) dysfunction (ejection fraction 39% +/- 9%) underwent resting 99mTc-MIBI tomography with initial (1 hr) and delayed (5 hr) images. Within 1 wk of MIBI imaging, all patients underwent rest-distribution 201Tl imaging. Eight patients also underwent two-dimensional echocardiography before and 5 +/- 3 mo after coronary revascularization. RESULTS: On the initial 99mTc-MIBI images, 302 myocardial segments were normal, 183 showed moderate and 197 severe reduction of tracer uptake. Of these 197 segments, 47 (24%) demonstrated increased tracer uptake (> or = 10% versus initial) on delayed images (from 43% +/- 8% to 60% +/- 8%, p < 0.001) and were considered as showing 99mTc-MIBI redistribution. These 47 segments were observed in 20 (65%) patients in whom 201Tl images detected viable myocardium in the same segments. In the eight patients studied before and after revascularization, 83% of segments with 99mTc-MIBI redistribution and abnormal LV function showed functional recovery after revascularization, while 96% of segments without 99mTc-MIBI redistribution did not show functional recovery. CONCLUSION: Resting 99mTc-MIBI redistribution frequently occurs in patients with chronic CAD. Acquisition of 99mTc-MIBI redistribution images enhances detection of viable myocardium and predicts functional recovery after revascularization.
Coronary Disease↗
[Morpho-functional diagnostic imaging in the assessment of viable myocardium in patients with ischemic heart disease. Correlations between myocardial perfusion and regional function of the left ventricle].
Forty patients (38 men and 2 women, mean age 56 +/- 9 years) with angiographic evidence of coronary artery disease underwent 201Thallium myocardial scintigraphy and two-dimensional echocardiography. 201Thallium uptake and echocardiographic regional ventricular function were studied in corresponding myocardial segments. On exercise-redistribution 201Thallium imaging, 308 segments (51% of the total) had normal Thallium uptake, 48 (8%) exhibited reversible defects and 244 (41%) irreversible defects. Of the latter 244 segments with irreversible defects, 114 (47%) exhibited increased tracer uptake (Re+) and 130 (53%) remained unchanged (Re-) after 201Thallium reinjection at rest. Regional ventricular function was significantly better in the segments with normal Thallium uptake than in the segments with reversible or irreversible defects (p < 0.001). Furthermore, the segments with irreversible defects Re- had impaired regional function compared to the segments with irreversible defects Re+ (p < 0.001). Coronary artery stenosis was significantly more severe in the segments with irreversible defects Re- (93 +/- 16%) than in those with reversible defects (81 +/- 20%) and with irreversible Re+ defects (80 +/- 20%) (both p < 0.001). In conclusion, in coronary artery disease patients, exercise-redistribution 201Thallium cardiac imaging with reinjection at rest can identify severely ischemic but still viable myocardium and may be particularly useful in the prognosis of such patients.
Adult↗
Ambulatory monitoring of left ventricular function during cardiopulmonary exercise tests in normal sedentary subjects.
UNLABELLED: Ambulatory monitoring (VEST) of left ventricular (LV) function is a useful and accurate method to measure cardiac function during exercise and rest. The aim of this study was to evaluate LV response to exercise in normal sedentary subjects. METHODS: Ten normal sedentary subjects underwent continuous ambulatory monitoring of LV function by VEST during upright bicycle exercise associated with combined analysis of pulmonary gas exchange. All parameters of LV function were measured in control conditions at rest, at the anaerobic threshold (point of nonlinear increase in ventilation relative to oxygen uptake) and at peak oxygen uptake (peak VO2). RESULTS: Heart rate and cardiac output significantly increased from control conditions to anaerobic threshold (p < 0.001) and from anaerobic threshold to peak VO2 (p < 0.001). Ejection fraction, end diastolic volume and stroke volume significantly increased from control conditions to anaerobic threshold (p < 0.001), showing no significant change from anaerobic threshold to peak VO2. Finally, end-systolic volume significantly decreased from control conditions to anaerobic threshold (p < 0.001), showing no significant change from anaerobic threshold to peak VO2. CONCLUSION: VEST is particularly useful in the evaluation of cardiac response to exercise in normal sedentary subjects, providing a better understanding of the spectrum of the normal LVEF response to exercise. Our data demonstrate that ejection fraction response to exercise is variable after anaerobic threshold, and a uniform increase is not necessarily expected in normal sedentary subjects.
Adult↗