CAMIRD/III: a revised version of the CAMIRD/II and MIRD-S packages for internal dose calculation: concise communication.

We describe the characteristics of the CAMIRD/III, a software package for the calculation of radiation dose from internally distributed radionuclides. The work concerns the preparation of a revised version of both CAMIRD/II, which uses prestored data of the specific absorbed-energy fraction, and MIRD-S, which uses the precalculated "S" values. Some improvement in the dose computation has been realized, for instance in the case of organs with walls, The software, written in FORTRAN IV, runs on an IBM 370/168 computer.

Performance characteristics of a whole-body positron tomograph.

This paper describes an investigation of some of the important physical characteristics of a whole-body positron tomograph consisting of two rings of bismuth germanate detectors of dimensions 5.6 mm X 30 mm X 30 mm (512/ring). The resolution applicable to in vivo imaging is six mm or more, depending on radionuclide and reconstruction filter and is very uniform over the field of view normally used. Axial resolution can be varied by moving side collimation (maximum approximately 16 mm FWHM with interplane septa). A simple scheme has been devised to correct for loss of true coincidence events with varying count rate based on the total random and multiple coincidence rates. It is concluded that correction for scattered radiation should be implemented for reliable quantitation.

An electronic "diaphragm" for the gamma camera, with adjustable zooming and offset.

We describe a new device for data acquisition from a gamma camera using an electronic spatial "diaphragm," with variable offset and zooming. The device, mainly applied to cardiac studies, permits selection of the desired part of the field of vision to be digitized and to zoom, before the computer acquisition. The spatial diaphragm spans 0.4-0.9 of the diameter of the FOV, and the amplification factor from 1.1 to 2.5.

Chromatographic identification in serum of endogenously radioiodinated thyroid hormones after iodine-131 whole-body scintigraphy in the follow-up of patients with differentiated thyroid carcinoma.

Patients with differentiated thyroid cancer (DTC) are conventionally followed with serial 131I whole-body scintigraphy (WBS) and serum thyroglobulin (hTg) assay. Given the 15%-20% incidence of discordant results, we developed a sensitive and specific procedure for monitoring such patients, based on the assumption that 131I uptake, even if too low to be detected by 131I WBS, could be assayed in serum as thyroid products (hTg, T3 and T4) endogenously labeled with 131I. Our study included 125 patients routinely monitored for tumor recurrence or for the persistence of functioning thyroid tissue after complete primary treatment for DTC (surgery and 131I ablation of remnants). A plasma sample, taken 72 hr after administering 131I for WBS was fractionated on a Sephadex-G25 superfine column by first eluting all of the radioactive species except the thyroid hormones and then the radioiodothyronines. The sensitivity and specificity of chromatography in detecting functioning thyroid tissue after primary treatment for DTC were 98.4% and 100% (accuracy 99.2%), respectively, versus 90.6% and 95.1% for 131I WBS (accuracy 92.8%) and 60.9% and 100% for hTg (accuracy 80%). Combining chromatography with serum hTg gave the highest gains in diagnostic performance (100% for all parameters). This chromatographic method can be used in addition to conventional procedures in the follow-up of patients with DTC and represents a highly sensitive test for assessing the results of 131I ablation of postsurgical remnants.

Simultaneous in vitro and in vivo validation of nitrogen-13-ammonia for the assessment of regional myocardial blood flow.

Measurement of myocardial blood flow by 13NH3 relies heavily on the assessment of both the input function and the variable tissue extraction fraction. In six open-chest dogs, myocardial and arterial 13NH3 activity was measured both by in vitro sampling and by in vivo positron emission tomography (PET). Regional myocardial blood flow was forced to vary in the range 0.2-5 ml/min/g and actual values were assessed by in vitro counting of 153Gd microspheres. The ammonia input function was processed by: (a) total curve integration; (b) curve integration for 2 min; (c) integral of a fitted curve (gamma variate in vivo and exponential of the downslope in vitro). Method C brought to regional flow values which best approximated microspheres data. The in vitro correlation allows for correcting in vivo values for the flow-dependent extraction fraction. The method can be easily applied for regional myocardial blood flow measurements with PET in human studies.

Tumor targeting by intra-arterial infusion of 5-[123I]iodo-2'-deoxyuridine in patients with liver metastases from colorectal cancer.

UNLABELLED: We previously showed the tumor-targeting potential of the 125I-labeled thymidine analog 5-iodo-2'-deoxyuridine (IUdR) injected intratumorally in patients with high tumor-cell kinetics. In this study, we evaluated the tumor incorporation of [123I]IUdR infused intra-arterially in patients with liver metastases from colorectal cancer. METHODS: Iodine-123-IUdR (110-300 MBq, 3-8 mCi, specific activity, 150-200 Ci/mumole) was infused into the hepatic artery of 16 patients with inoperable liver metastases over 30-45 min through a permanent intra-arterial catheter. A dynamic sequence during infusion, spot images, whole-body scans and SPECT acquisitions were recorded up to 42 hr. Blood and urine samples were obtained for biodistribution and HPLC analyses. RESULTS: In the 14 patients with adequate tumor perfusion patterns, tumor uptake reached 2%-17.6% ID at the end of infusion. After a washout phase that lasted 18-20 hr, incorporated radioactivity remained steadily associated with the tumor lesions until at least 42 hr after infusion (about 1.4%-11.1% ID). HPLC analysis indicated a virtually 100% first-pass hepatic deiodination of unincorporated [123I]IUdR (about 80%-95% ID recovered in the 42-hr urine). No significant uptake was detected in the bone marrow or in other normal dividing tissues. CONCLUSION: These results encourage further studies to enable dosimetric estimates, optimization of dose regimens, and examination of the therapeutic potential of Auger-electron-emitter-labeled IUdR in cancer therapy utilizing this type of approach.

Myocardial perfusion abnormalities in chronic Chagas' disease as detected by thallium-201 scintigraphy.

Most patients with chronic Chagas' heart disease complain of chest pain. The pathophysiology of this symptom is unknown, although myocardial necrosis and fibrosis are frequent necropsy findings and cardiac autonomic impairment is a prominent feature of the disease. To evaluate the possibility of an ischemic cause for these abnormalities in 23 patients (18 men, aged 32 to 60 years, mean 42) with chronic Chagas' disease complaining of chest pain, thallium-201 myocardial scintigraphy was performed after maximal effort and 4-hour redistribution. Regional wall motion was assessed by radionuclide and contrast angiography. Heart rate responses to sinus respiratory arrhythmia, atropine, phenylephrine and Valsalva maneuver were evaluated in all patients and in 22 normal control subjects. Coronary angiography was performed in 16 patients. Only 1 patient had chest pain and no ischemic electrocardiographic changes occurred in any case during the effort test. Scintigraphic analysis of 7 segments per patient showed perfusion defects in at least 1 segment in all patients. Of 161 myocardial segments 16 showed fixed, 10 reversible, and 22 paradox defects (reverse redistribution). The majority (75%) of the fixed perfusion defects occurred in dyssynergic regions, whereas reverse redistribution predominated in regions with normal wall motion (82%). The reversible defects were present in normal or mildly hypokinetic regions. Markedly impaired parasympathetic cardiac control was present but no significant coronary abnormalities were seen in any of the 16 patients undergoing angiography. It is concluded that whereas fixed defects are likely to correspond to fibrotic or necrotic lesions, reversible and paradox perfusion defects may be caused by regional flow or metabolism derangements, possibly related to abnormal parasympathetic control of the coronary microcirculation.

Intrapleural liquid flow down a gravity-dependent hydraulic pressure gradient.

We studied the vertical movement of 2 mg technetium-labeled albumin injected intrapleurally in 0.5 ml saline (15% of pleural liquid volume) in eight spontaneously breathing anesthetized dogs subject to a sudden change in posture (prone to supine or vice versa). The albumin movements were evaluated through a large field gamma camera placed laterally to the animal and detecting total (AT) and regional activities from two superimposed equal areas (At and Ab, top and bottom, respectively). The At/Ab ratio decreased from 2.1 to 1.3 in four animals up to 20 min from the change in posture and from 0.9 to 0.5 in four more animals studied from 50 to 90 min from turning maneuver. The rate of change in At and Ab was similar in the two groups of animals and unaffected by the acquisition posture. AT decreased by 7.7 and 3.5% for the two groups, respectively, reflecting albumin clearance from the pleural space. The opposite time course of regional activities and the independence of their rate of change of the At/Ab ratio and of the animal posture suggest a top-to-bottom albumin transfer occurring through a bulk flow of liquid estimated at 0.006 ml.kg-1.h-1. The data are consistent with a measured vertical pleural liquid pressure gradient that does not reflect a hydrostatic condition.

Tc 99m-Sestamibi scintimammography in the differentiation of benign and malignant breast microcalcifications.

The capability of the mammography-scintimammography combination to distinguish between benign and malignant isolated clusters of breast microcalcifications is discussed. Scintimammography using Tc 99m-Sestamibi was performed in 97 women with an isolated cluster of microcalcifications on mammograms. Seventy-two women had final histopathologic diagnoses (24 cancer and 48 benign pathology). The other 25 patients had follow-up to 3 years. The results of mammography, scintimammography and mammography-scintimammography combination were divided into five groups, based on the suspicion of malignancy. The sensitivity, specificity, false negative fraction, false positive fraction, predictive positive value, predictive negative value and diagnostic accuracy were calculated varying the diagnostic threshold. The Receiver Operating Characteristic (ROC) statistical technique was employed to compare the diagnostic value of mammography to mammography-scintimammography combination. The area under the ROC curves was calculated by the Wilcoxon statistic without any hypothesis on data distribution. The detected difference between areas under the mammography ROC curve (area=0.854, standard error=0.049) and mammography-scintimammography ROC curve (area=0.897, standard error 0.033) was statistically significant (P>0.05, one tail). The area under a ROC curve represents the probability that a randomly chosen diseased or non-diseased subject could be correctly classified. From this point of view this paper demonstrates that, if properly used, scintimammography can add to mammography in the characterization of an isolated cluster of microcalcifications, even if it is not able to replace FNAB and core biopsy.

Investigation on the iodination reaction of methylene blue by liquid chromatography-mass spectrometry with ionspray ionisation.

Radioactive iodine (131I and 123I) labelled methylene blue is used for the early diagnosis of melanoma metastases. We studied the iodination reaction of methylene blue (using "cold" iodine) in order to characterise the iodination product(s) as far as number and position of iodine atoms introduced on the aromatic ring(s) is concerned. The reaction was carried out under the same experimental conditions used for the radioactive one, that is in a large excess of methylene blue. The ionspray HPLC-MS analysis of the reaction mixture showed that the iodinated methylene blue was present only in a very small amount and the main iodinated product was a demethylated one, coming out from the iodination of an impurity azure B. We also studied the iodination reaction of azure B in order to better explain the reaction pathway. Commercial azure B contains impurities of methylene blue and all the possible demethylated derivatives. HPLC-MS analysis of the reaction mixture allowed a complete characterisation of the iodinated and bis-iodinated products.

Gamma probe-guided thoracoscopic surgery of small pulmonary nodules.

Video-assisted thoracic surgery (VATS) is an interesting and emerging procedure for the diagnosis and treatment of peripheral pulmonary nodules. We developed a new radioguided surgical technique for the detection during VATS of pulmonary nodules smaller than 2 cm, situated deep in the lung parenchyma and neither visible nor palpable with endoscopic instruments. The procedure is divided into two phases. Two hours before surgery 0.3 ml of a solution composed of 0.2 mL of 99mTc-labeled human serum albumin microspheres (5-10 MBq) and 0.1 mL of non-ionic contrast is injected into the lesion under CT guidance. Then the patient is submitted to VATS. During thoracoscopy a collimated probe of 11 mm diameter connected to a gamma ray detector is introduced via an 11.5 mm trocar and the pleural surface of the suspected area is scanned. A hot spot indicates the presence of the radiolabeled nodule and hence the area to be resected. We treated 39 patients with small pulmonary nodules (mean size, 8.3 mm; range, 4-19 mm). The patients were 27 men and 12 women (mean age, 60.8 years; range, 13-80 years). Nineteen patients had a history of synchronous or metachronous malignancy. In all cases the nodule was detected and resected and the resection margins were pathologically free of tumor. Histological examination showed 21 benign and 18 malignant lesions (7 metastases and 11 primary lung cancers). Nine patients with a frozen section-based histopathological diagnosis of lung cancer without functional contraindications underwent a completion lobectomy by open surgery in the same surgical session. In conclusion, the radiolocalization of small pulmonary nodules by gamma probe during VATS is a safe and easy procedure, with fewer complications and a lower failure rate than other localization techniques.

Detection of melanoma cells in peripheral blood and sentinel lymph nodes by RT-PCR analysis: a comparative study with immunohistochemistry.

The presence of lymph node metastases is the best prognostic factor for predicting relapse or survival in melanoma patients. It has been demonstrated that melanoma metastases spread through the first lymph node(s) draining the tumor (sentinel lymph node, SN) to the lymphatic system and that detection of melanoma cells in peripheral blood directly correlates with prognosis in melanoma. To identify lymph node metastases and circulating melanocytes, we developed a single-step reverse transcriptase-polymerase chain reaction assay (RT-PCR) for detection of two melanoma-specific markers: the tyrosinase gene, which encodes an enzyme associated with melanin synthesis, and melanoma antigen-related T-cells, which are present in tumor infiltrating T-lymphocytes. This method detects two tumor cells in a background of 10(7) lymphocytes. Thirty patients with stage I-IV cutaneous melanoma entered the study. Blood samples were taken preoperatively, one month after excision of the primary melanoma lesion and the SN or total lymphadenectomy, and before the start of chemotherapy and every three months thereafter in metastatic patients. SNs were collected from 22 patients, bisected and analyzed by RT-PCR and routine pathological and immunohistochemical tests. The preliminary results indicate that RT-PCR for melanoma markers is a sensitive and valuable method for the detection of micrometastases and for early diagnosis and staging of melanoma.

Evaluation of reconstructed scatter fraction on PET images.

This paper describes a procedure proposed for the quantitative evaluation of the influence of the scattering noise on the reconstructed PET images. Applying the same experimental procedure used to evaluate the Scatter Fraction (SF) on the sinograms obtained measuring line sources within a uniform scattering medium, the method here proposed permits the computation, after reconstruction, of a derived index of the SF i.e. the Reconstructed Scatter Fraction (RSF). This offers the advantage of providing an estimate of the scatter noise directly on the images obtained in the same processing conditions as during the in vivo human studies. Comparative data of SF and RSF are reported as well as the effect of varying the filter function and of the measured attenuation correction on the RSF. The preliminary results obtained show that the values of the reconstructed scatter fraction are closer to the SF ones when this last is computed only in the cylinder region and the RSF is computed on images reconstructed with a ramp filter.

User-friendly image processing software tools: general purpose features and application to the correlation of PET-CT brain images.

An interactive software package, performing some useful general purpose image processing operations and being used as a tool for the problem of the anatomical correlation of PET brain images, is under development. The software is developed as a comprehensive tool with a graphic user-interface allowing the display of the processed images through the use of a variety of colormaps. The implemented routines perform a lot of processing operations on the images: a) Local image processing, i.e. smoothing and sharpening, contours extraction, interactive expansion, shrinking and thresholding of the gray scale, histogram equalization. b) ROI handling, i.e., ROI drawing and computing, transformation of an image to a ROI, ROI editing. c) Additional operators include frequency space image processing such as FFT.

Measurement of resolution and recovery in recent generation positron tomographs.

In positron tomographic images, the ability to differentiate closely lying structures, the spillover of activity from a region into adjacent regions and the reduction in apparent isotope concentration in small structures are all dependent on spatial resolution. Resolution in the reconstructed image is affected by (i) detector size, (ii) the spatial sampling used (e.g. stationary, wobble), (iii) the amount of smoothing in the reconstruction process (or subsequent to reconstruction) and (iv) the image pixel size. Under ideal conditions, modern commercial tomographs can produce a reconstructed spatial resolution of 5 mm or less. However, this is rarely realizable in a clinical study due to the inadequacy of counting statistics and the amplification of statistical noise. In practice, a smoother filter has to be used. This paper presents a summary of practical measurements of spatial resolution, and the related count recovery, performed on recent generation positron tomographs. It is intended to contribute to the definition of methods of measuring these parameters which is part of an on going concerted action in positron tomography supported by the European Commission.

A non-invasive, quantitative method to demonstrate the early effects of therapy in acute pulmonary embolism.

The objective of this study was to quantify the changes in pulmonary perfusion due to therapy for pulmonary embolism (PE). To this end, seven consecutive patients (five men, two women; mean age 64+/-10 years) were studied. After basal pulmonary arteriography had demonstrated the presence of massive PE, patients were injected intravenously with 4 mCi of technetium-99m-labelled human albumin microspheres and were treated soon thereafter with a 2-h infusion of either alteplase 100 mg (five patients) or heparin 1,750 IU/h (two patients). Then, a second pulmonary arteriography study was obtained, and soon afterwards a single-photon emission tomographic (SPET) perfusion scan was performed. Immediately thereafter, a second intravenous injection of 4 mCi of 99mTc-labelled microspheres was administered, followed by a second SPET scan. At the end of the study, the perfusion changes due to therapy were quantified by subtraction of the images of the two SPET studies; the reperfused areas could be visualised and the volumes of reperfusion quantified. This study demonstrates the validity of a newly devised, relatively rapid and non-invasive method for quantification of the early effects of therapy on pulmonary perfusion in patients presenting with acute PE.

Pleural liquid pressure gradients and intrapleural distribution of injected bolus.

In supine anesthetized dogs we measured pleural liquid pressure (Pliq) in mediastinal, diaphragmatic, apical, and costal regions at different lung heights during eupneic breathing. At end expiration and at a given height, Pliq was similar in the costal and apical regions, but it was lower in the diaphragmatic and mediastinal compartments. Inspiratory swings toward lower values were progressively greater with increasing height and moving from costal to apical, diaphragmatic and mediastinal compartments. Thus during inspiration, at any height, the costomediastinal and costodiaphragmatic Pliq difference increased while a costoapical difference developed. One minute after injection of 0.5-1 ml of saline at different points within the cavity, end-expiratory liquid pressure became higher on the average by 0.45, 1.55, and 0.55 cmH2O in the apical, mediastinal, and diaphragmatic compartments, respectively, while no change was observed on costal side. These results suggested liquid accumulation in the compartments displaying a lower Pliq. This was confirmed by following, with a gamma camera, on a frontal projection of the lung, the intrapleural distribution of a bolus containing 99mTc-labeled albumin injected at various places.

[111In-DTPA-D-Phe]-octreotide scintigraphy in functioning and non-functioning pituitary adenomas.

Scintigraphy with [111In-DTPA-D-Phe]-octreotide is a recently developed technique for imaging somatostatin receptors in many neuroendocrine tumors. A good correlation between high [111In-DTPA-D-Phe]-octreotide uptake and the response to octreotide therapy has been proved in TSH- and GH-secreting pituitary adenomas, while few and conflicting scintigraphic data on somatostatin receptors in non-functioning tumors have been reported in the literature. The present study presents the results obtained with [111In-DTPA-D-Phe]-octreotide scintigraphy in thirteen patients with GH-secreting pituitary adenoma, four patients with inappropriate TSH-secretion and twelve patients with non-functioning pituitary adenoma. Twelve out of the 13 patients with GH-secreting pituitary adenomas had a positive scan; moreover, in 5/6 patients with a GH-secreting microadenoma (tumor size range 5-8 mm) a positive scan was found. Two TSH-secreting macroadenomas had a positive scan while a negative scan was obtained for a TSH-secreting pituitary microadenoma and in a patient with non-neoplastic, inappropriate secretion of TSH. Finally, only 2/12 patients with non-functioning pituitary adenoma showed a positive scan. In conclusion, [111In-DTPA-D-Phe]-octreotide scintigraphy is a useful tool to confirm the presence of somatostatin receptors in selected patients with GH- and TSH-secreting pituitary adenoma. The role of [111In-DTPA-D-Phe]-octreotide scintigraphy in non-functioning pituitary tumors remains to be established, but it could be useful for octreotide treatment in patients who refuse surgery or who are poor surgical candidates.

Relationship between extent of pulmonary emphysema by high-resolution computed tomography and lung elastic recoil in patients with chronic obstructive pulmonary disease.

We investigated the relationship between the extent of pulmonary emphysema, assessed by quantitative high-resolution computed tomography (HRCT), and lung mechanics in 24 patients with chronic obstructive pulmonary disease (COPD). The extent of emphysema was quantified as the relative lung area with CT numbers < -950 Hounsfield Units (HU). Patients with COPD had severe airflow obstruction (FEV(1) 35 +/- 15% pred) and severe reduction of CO diffusion constant (DCO/VA 37 +/- 19% pred). Maximal static elastic recoil pressure (Pst(max)) averaged 54 +/- 24% predicted, and the exponential constant K of pressure-volume curves was 258 +/- 116% predicted. Relative lung area with CT numbers < -950 HU averaged 21 +/- 11% (range 1 to 38%). It showed a highly significant negative correlation with DCO/VA (r = -0.84, p < 0.0001), a weak correlation with FEV(1)% predicted, and no correlation with either Pst(max) or constant K. A significant relationship was found between the natural logarithm of K and the full width at half maximum of the frequency distribution of CT numbers, taken as an index of the heterogeneity of lung density (r = 0.68, p < 0.0005). We conclude that currently used methods of assessing the extent of emphysema by HRCT closely reflect the reduction of CO diffusion constant, but cannot predict the elastic properties of the lung tissue.

A reappraisal of the bladder cumulative method as a reliable technique for the measurement of glomerular filtration rate.

In order to quantify the decline in renal function, repeated measurements of GFR are necessary. The conventional procedure is cumbersome and time expending so that alternative clearance techniques are needed. We propose a simple isotopic technique for measuring GFR by 99mTc-DTPA and external counting of the bladder by gamma camera (bladder cumulative method). This consists in the measurement by external counting of the amount of labelled filtration marker accumulated in the bladder after intravenous bolus injection. In 36 adult patients with all degrees of renal impairment (serum creatinine 0.9-9.3 mg/dL) GFR was measured twice, once by the conventional method (continuous i.v. infusion of the filtration marker and urine collection by spontaneous voiding) and once by the bladder cumulative method. 99mTc DTPA was used in performing both methods. A satisfactory agreement was found between GFR measured by bladder cumulative method (BCM) and by conventional method (CM). The BCM averaged 60.0 +/- 36.7 mL/min and the CM +/- SD averaged 62.8 +/- 36.6 mL/mm. The ratio BCM/CM +/- SD was 0.95 +/- 0.14 (y = 0.94x + 1.14; r = 0.94). Considering the 17 patients with renal insufficiency (GFR < 60 mL/min) an even better agreement between the two methods was found. In these patients the BCM averaged 28.4 +/- 17.2 mL/min; the CM averaged 29.1 +/- 16.6 mL/min; and the ratio BCM/CM was 0.96 +/- 0.08 (y = 1.03x - 1.47; r = 0.99). The day-to-day variability of BCM, studied in another 11 patients, was lower than that of creatinine clearance (variation coefficient for duplicate measurements: 7.18 +/- 6.65 SD for BCM, 15.68 +/- 8.80 SD for CM, p < 0.01). The bladder cumulative method is a simple procedure for the accurate measurement of GFR, in particular in patients with renal insufficiency. It represents a reliable tool for estimating the decline in renal function.