Intrinsic dual-energy processing of myocardial perfusion images.

UNLABELLED: We have developed a software-based method for processing dual-energy 201TI SPECT emission projection data with the goal of calculating a spatially dependent index of the local impact of gamma-ray attenuation. We refer to this method as intrinsic dual-energy processing (IDEP). METHODS: IDEP exploits the differential attenuation of lower energy emissions (69-83 keV) and higher energy emissions (167 keV) resulting from the decay of 201TI to characterize the relative degree of low-energy gamma-ray attenuation throughout the myocardium. In particular, IDEP can be used to estimate the relative probability that a low-energy gamma-ray emitted from a particular region of the myocardium is detected during the acquisition of SPECT projection data. Studies on phantoms and healthy human volunteers were performed to determine whether the IDEP method yielded detection probability images with systematic structure visible above the noise of these images and whether the systematic structure in the detection probability images could be rationalized physically. In patient studies, the relative regional detection probabilities were applied qualitatively to determine the likely effects of attenuation on the distribution of mapped photon emissions. RESULTS: Measurements of the detection probability in uniform phantoms showed excellent agreement with those obtained from computer simulations for both 180 degrees and 360 degrees acquisitions. Additional simulations with digital phantoms showed good correlation between IDEP-estimated detection probabilities and calculated detection probabilities. In patient studies, the IDEP-derived detection probability maps showed qualitative agreement with known nonuniform attenuation characteristics of the human thorax. When IDEP data were integrated with the findings on the emission scan, the correlation with coronary anatomy (known in 6 patients and hypothesized on the basis of clinical and electrocardiographic parameters in 5 patients) was improved compared with evaluating the mapped emission image alone. CONCLUSION: The IDEP method has the potential to characterize the attenuation properties of an object without use of a separate transmission scan. Coupled with the emission data, it may aid coronary diagnosis.

Phase I dose escalation of 131I-metaiodobenzylguanidine with autologous bone marrow support in refractory neuroblastoma.

PURPOSE: The analogue 131I-metaiodobenzylguanidine (MIBG), which is specifically targeted to neuroblastoma cells, may provide more effective and less toxic treatment for neuroblastoma than conventional external-beam radiotherapy. We report a dose escalation study of 131I-MIBG to define dose-limiting toxicity without and with autologous bone marrow support. PATIENTS AND METHODS: Thirty patients with relapsed neuroblastoma were treated in groups of six with escalating doses of 3 to 18 mCi/kg of 131I-MIBG. After rapid escalation in the first three patients treated at 3 to 6 mCi/kg, treatment was escalated in 3-mCi/kg increments from 9 to 18 mCi/kg. Autologous tumor-free bone marrow was cryopreserved in all patients receiving 12 mCi/kg and more. Toxicity and response were assessed. RESULTS: Eighty percent of patients who received 12 mC/kg or more experienced grade 4 thrombocytopenia and/or neutropenia. Dose-limiting hematologic toxicity was reached at 15 mCi/kg, at which level two of five assessable patients required bone marrow reinfusion for absolute neutrophil count (ANC) of less than 200/microL for more than 2 weeks, and four of nine at the 18-mCi/kg level. Prolonged thrombocytopenia was common, with failure to become platelet-transfusion independent in nine patients. One patient with extensive prior treatment developed secondary leukemia and three became hypothyroid. Responses were seen in 37% of patients, with one complete response (CR), 10 partial response (PR), three mixed response, 10 stable disease, and six progressive disease. The minimum dose of 131I-MIBG for 10 of the 11 responders was 12 mCi/kg. CONCLUSION: Treatment with 131I-MIBG has mainly hematologic toxicity, which can be abrogated with bone marrow rescue. The high response rate in refractory disease suggests that this agent may be useful in combination with myeloablative chemotherapy and autologous stem-cell rescue to improve outcome in advanced neuroblastoma.

Contradictory renal function measured with mercaptoacetyltriglycine diuretic renography in unilateral hydronephrosis.

PURPOSE: We studied apparently supranormal renal function in hydronephrotic kidneys, as measured by 99mtechnetium mercaptoacetyltriglycine renography. MATERIALS AND METHODS: We retrospectively reviewed the clinical history, ultrasonography and renography of 29 children. RESULTS: Of the 29 children 7 had greater than 50% relative function in the hydronephrotic kidney. This finding was independent of patient age, gender, degree of hydronephrosis or obstructive pattern. Of these 7 cases 6 occurred on the right side (p < 0.05 versus a large registry). CONCLUSIONS: In most cases supranormal renal function is caused by a technical problem, likely the inadequate background subtraction of mercaptoacetyltriglycine in the liver.

The effect of newer generation lithotripsy upon renal function assessed by nuclear scintigraphy.

PURPOSE: We studied the effect of second generation lithotripsy on renal function. MATERIALS AND METHODS: We evaluated 42 patients with unilateral renal calculi by nuclear renography, serum creatinine levels, renal ultrasonography and plain radiographs. RESULTS: There was no significant change in glomerular filtration rate at 1 or 3 months. Split function of the treated kidneys was lower at 1 month (mean 47.2%, p = 0.01) and 3 months (47.3%, p = 0.01) than before treatment (49.1%). A greater than 5% decrease in split function of the treated kidney occurred at 1 month in 6 patients (16.2%) and at 3 months in 3. Of the patients 23 (62.2%) were stone-free and 11 had residual fragments less than 4 mm., with a 19% retreatment rate for an overall success rate of 91.9%. CONCLUSIONS: Newer generation lithotriptors may limit renal damage while permitting satisfactory treatment of renal calculi.

Normal cerebellar MIBG localization. Implications in the interpretation of delayed scans.

In the I-131 MIBG scans of 14 patients with neuroblastoma (86%) or pheochromocytoma/paraganglioma (14%) that were studied more than 48 hours after administration of the radiopharmaceutical, 12 (86%) had discernible cerebellar MIBG localization. A few had midbrain or diffuse cerebral uptake as well. None of the patients had cerebellar or other central nervous system signs or symptoms, and the localization is consistent with the known distribution density of central nervous system catecholamine receptors. This suggests that cerebellar MIBG localization is normal in delayed scans and that it should not be confused with neuraxial metastasis of adrenergic neuronal neoplasms.

Normal cholescintigram in In-111 WBC positive acute acalculous cholecystitis. The converse photopenic 'rim' sign.

The authors report a case of a patient with acute acalculous cholecystitis whose cholescintigram was negative, but showed a pericholecystic photopenic halo. The diagnosis was confirmed by an In-111 WBC scan and histopathology.

Urolithoscintigraphy: preliminary report of a new imaging modality for urolithiasis.

We investigated the use of bisphosphonates, analogs of pyrophosphate that bind to mineralized tissue, to image renal calculi in vivo. Twenty stone-bearing kidneys in 15 patients without urinary obstruction were studied. 99mTechnetium-methylene diphosphonate was injected intravenously followed by 20 mg of furosemide 4 hours later, and images were obtained by gamma counter for 30 minutes. Areas of increased uptake corresponded with the sites of calculi, and even small or radiolucent calculi were easily seen. Counts in the region of each kidney, the L4 vertebral body, and a background area were combined to calculate a scintigram index (SI) for each kidney. The mean SI of the stone-bearing kidneys was 4.8 +/- 3.5 v 1.3 +/- 0.4 for the normal kidneys. There was correlation of the SI with stone composition and size but not with radiographic density. After correction for size, the SI of stone-bearing kidneys remained significantly higher than the SI of normal kidneys, but the differences between calculi of different compositions were diminished. Nonetheless, high SI values were associated with soft types of calculi and low values with hard types. Future investigations will reveal if this association is constant and if there is any relation between bisphosphonate uptake and response to lithotripsy. The sensitivity of urolithoscintigraphy to image small or radiolucent calculi may make it an effective technique for the assessment of residual fragments after lithotripsy.

Clinical utility of bone scan features of pleural effusion: sensitivity and specificity for malignancy based on pleural fluid cytopathology.

UNLABELLED: Asymmetric chest activity with malignant and benign pleural effusions has been described in bone scans. However, the clinical utility of this finding is not elucible from the literature. We developed specific scintigraphic criteria for malignant pleural effusion and retrospectively assessed their sensitivity and specificity in a group of patient scans. METHODS: Pleural fluid was submitted for cytopathology from 850 patients over a 5-yr period. Bone scans were done within 2 mo of the thoracentesis in 74 patients. As a consensus panel, we reread the scans and reviewed the cytology. RESULTS: The effusions were cytologically malignant in 25/74 patients (34%), indeterminate in 9/74 (12%) and benign in 40/74 (54%). Based on cytopathology, malignant pleural effusions were detected by bone scans with a sensitivity of 34%-50% and a specificity of 78%-89%; true sensitivity and specificity was somewhere in between averaging 42% (95% confidence interval 24%-60%) and 84% (95% confidence interval 73%-95%), respectively. CONCLUSIONS: The bone scan is frequently the first examination suggesting pleural metastasis, and when it is detected it should be pursued beyond pleural fluid cytology, if negative or indeterminate.

Optimized diagnostic strategy for neuroblastoma in opsoclonus-myoclonus.

Infantile myoclonic encephalopathy (opsoclonus-myoclonus or IME) is a rare clinical syndrome associated with occult neuroblastoma in 20%-50% of all cases. IME is the initial presentation of neuroblastoma in 1%-3% of children. Imaging approaches including chest radiography and abdominal computed tomography (CT) have been proposed to detect neuroblastoma in IME. Metaiodobenzylguanidine (MIBG) is highly effective in the detection of neuroblastoma. These scans can identify both soft-tissue and skeletal lesions anywhere in the body. Our purpose was to attempt to determine the best screening method for detection of occult neuroblastoma in patients with IME. Records of all neuroblastoma patients from 1983 to May 1991 were reviewed. Four cases of IME with neuroblastoma were identified in which imaging studies included an MIBG scan. All four patients had positive MIBG scans (100%) while only two had masses on initial CT (50%). In the three patients initially evaluated by traditional methods, the mean time to diagnosis and the mean number of advanced radiologic studies were 7.5 mo and 7.3 studies respectively. The patient screened with MIBG had only cranial and abdominal CT prior to surgery. Although based on a limited number of patients, results suggest that MIBG may prove to be a useful screening procedure in patients with IME. Traditional imaging modalities can then be directed to evaluate sites of disease identified by MIBG scans.

Practical considerations in the scintigraphic evaluation of endocrine hypertension. The adrenal cortex and medulla.

A nuclear scan maps the distribution of a radiopharmaceutical that is specific for a physiologic property of a targeted tissue. As such, it is not limited by the anatomic changes necessary for CT and MR scans. It is just because of this that maps of specific metabolic precursors of adrenal medullary and cortical hormones offer information crucial to the therapeutic strategy of endocrine hypertension. NP-59 and MIBG scans can specify the nature of abnormalities revealed by anatomic images and because of the ease of surveying the whole body can give transcendent information about lesions remote from the adrenals. In instances when the origin of endocrine hypertension is not forthcoming from CT or MR imaging or when the anatomic and biochemical findings are in conflict, NP-59 or MIBG can almost always provide the answer.

Efficacy of metaiodobenzylguanidine as a scintigraphic agent for the detection of neuroblastoma.

RATIONALE AND OBJECTIVES: Metaiodobenzylguanidine (MIBG) has been shown to be both sensitive and highly specific for the detection of neuroblastoma. However, controversy surrounds its sensitivity in detecting neuroblastoma when compared with radionuclide (technetium 99m-methylene diphosphonate [99mTc]-MDP) bone scans. Because a diagnostic test ideally should be easy to interpret in addition to being sensitive and specific, this study aims to determine the most efficacious scintigraphic agent for diagnostic use in neuroblastoma. METHODS: Twenty patients with neuroblastoma had a total of 26 paired MIBG and 99mTc-MDP bone scans obtained less than 4 weeks apart. Each study was evaluated independently of its counterpart by six separate observers (3 experienced and 3 inexperienced in MIBG scintigraphy) to determine the presence or absence of disease and the tumor burden. RESULTS: Inexperienced observers reported more confidence in their interpretations of 99mTc-MDP bone scans; however, seven false-positive bone scans were reported. Using MIBG, all true-positive and true-negative scans, as well as significantly more sites of both primary and metastatic disease, were identified by all observers. CONCLUSION: This study suggests that MIBG is the more efficacious agent for the scintigraphic evaluation of neuroblastoma.

Neuroblastoma: dose-related sensitivity of MIBG scanning in detection.

Iodine-131 metaiodobenzylguanidine (MIBG) has shown effectiveness as a systemic radiotherapeutic agent in neuroblastoma. The authors postulated a likely dose-related relationship of MIBG sensitivity when it was administered for neuroblastoma detection. They studied this relationship in neuroblastoma patients who underwent scanning after receiving diagnostic and therapeutic doses of MIBG in temporal proximity. Seven patients with stage IV disease received a total of 14 therapeutic administrations of I-131 MIBG (150-350 mCi [5,550-12,950 MBq]/m2 per treatment). Posttherapy scans were obtained at 3 and at 5-7 days. Diagnostic MIBG scans had been obtained no more than 4 weeks before the start of therapy. Use of diagnostic MIBG scanning led to underestimation of the tumor burden by 50% compared with use of posttherapy scanning. This difference may be an important consideration in selecting therapeutic strategies for individual patients. It further suggests that use of much larger diagnostic doses of MIBG is a rational strategy in histologically confirmed cases of advanced disease.

Scintigraphic assessment of MIBG uptake in globally denervated human and canine hearts--implications for clinical studies.

To further characterize the behavior of metaiodobenzylguanidine (MIBG) in the myocardium and to test the hypothesis that the denervated heart would show normal early uptake on MIBG due to non-neuronal localization, we examined the early and late distribution of 123I-labeled MIBG in normal and globally denervated canine and human hearts. Canine hearts were denervated by intravenous injections of 6-hydroxydopamine, while patients were studied a mean of 4.3 mo following cardiac transplantation. Results in denervated hearts were compared to normal controls. Normal hearts showed prominent MIBG uptake on initial 5-min and 3-hr delayed images. Globally denervated canine hearts showed prominent uptake on initial images and absence of localization on delayed images, indicating complete washout of non-neuronally bound radionuclide. The transplanted human hearts showed no localization of MIBG on either early or delayed images. These results suggest that the non-neuronal uptake mechanism (uptake 2) is not significant in human myocardium. This finding has significant implications for interpreting the myocardial behavior of MIBG in various pathologic situations such as dilated cardiomyopathy.

Bilateral testicular neuroblastoma. Scintigraphic depiction and therapy with I-131 MIBG.

The authors describe a 29-year-old man who had a 16-year history of neuroblastoma and uncommon manifestations. At age 13, he was diagnosed with stage III retroperitoneal ganglioneuroblastoma that was resected. Ten years later, bilateral testicular enlargement and a pelvic mass from infiltration of the neuroblastoma became palpable. Metastatic involvement was depicted with MIBG, a radiotracer that concentrates in tissues of the sympathetic nervous system. Using I-131 MIBG, the tumors were treated with therapeutic doses of radiation and a partial response was obtained. This case is unique because of the massive degree of bilateral testicular infiltration and its occurrence as a late manifestation of neuroblastoma in early adulthood.