Improvement of non-small-cell lung cancer staging by means of positron emission tomography.

BACKGROUND: Exact staging of ipsi- and contralateral mediastinal lymph-node metastases (N 1/2 vs. N3) is essential for the therapeutic strategy in non-small-cell lung cancer (NSCLC). CT and mediastinoscopy are the standards of reference for N staging. However, even with these combined measures the extent of invasion of mediastinal lymph nodes can remain vague. 18FDG Positron Emission Tomography (18FDG-PET) has recently been shown to detect invaded nodes with high accuracy. The purpose of this study was to evaluate 18FDG-PET as an aid in N staging. METHODS: 27 patients with suspected NSCLC were clinically staged by means of CT, bronchoscopy, mediastinoscopy, and bone scintigraphy. Additionally, 18FDG-PET was performed preoperatively for analysis of topography of invaded lymph nodes. CT and 18FDG-PET were evaluated in a blinded fashion. Surgical therapy was performed with radical lymphadenectomy. CT N staging as well as PET N staging results were compared with the pathological diagnoses (pTN). Specificity, sensitivity, and accuracy of CT and PET in N staging were calculated. RESULTS: 14 squamous-cell carcinomas, 10 adenocarcinomas, and 3 non-malignant tumors were found. In 8 patients no invasion was found (N0), in 13 patients an ipsilateral invasion (N1/2), and in 3 patients a contralateral invasion (N3). In the correct detection of N1/2 the sensitivity of CT and of PET was 0.77, the specificity of CT and of PET was 0.79. The accuracy of CT was 0.74 and of PET 0.78. By combining CT and PET accuracy was 0.85. CONCLUSIONS: Adequate preoperative LN staging is possible with both CT and 18FDG-PET. The accuracy, however, can be improved by a combination of CT and 18FDG-PET.

Fluorine-18 fluorodeoxyglucose positron emission tomography in thyroid cancer: results of a multicentre study.

The aim of this multicentre study was to evaluate the clinical significance of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in differentiated thyroid carcinoma and to compare the results with both iodine-131 whole-body scintigraphy (WBS) and technetium-99m 2-methoxyisobutylisonitrile (MIBI) or thallium-201 chloride (Tl) scintigraphy. Whole-body PET imaging using FDG was performed in 222 patients: 134 with papillary tumours, 80 with follicular tumours and 8 with mixed-cell type tumours. Finally, for each case an overall clinical evaluation was done including histology, cytology, thyroglobulin level, ultrasonography, computed tomography and subsequent clinical course, to allow a comparison with functional imaging results. Sensitivity of FDG-PET was 75% and 85% for the whole patient group (n = 222) and the group with negative radioiodine scan (n = 166), respectively. Specificity was 90% in the whole patient group. Sensitivity and specificity of WBS were 50% and 99%, respectively. When the results of FDG-PET and WBS were considered in combination, tumour tissue was missed in only 7%. Sensitivity and specificity of MIBI/Tl were 53% and 92%, respectively (n = 117). We conclude that FDG-PET is a sensitive method in the follow-up of thyroid cancer which should be considered in all patients suffering from differentiated thyroid cancer with suspected recurrence and/or metastases, and particularly in those with elevated thyroglobulin values and negative WBS.

Fluorine-18-FDG and iodine-131-iodide uptake in thyroid cancer.

UNLABELLED: We conducted a prospective study to define the sensitivity of 131I scintigraphy and 18FDG PET whole-body scanning in the detection of thyroid cancer and metastases. METHODS: Forty-one patients with differentiated thyroid carcinoma who underwent thyroidectomy and 131I elimination of the remaining thyroid were studied by 18FDG whole-body PET in 52 examinations and by 131I whole-body scanning. RESULTS: Combined 18FDG and 131I imaging resulted in a sensitivity of about 95%, with alternating uptake of 131I and 18FDG in the metastases: 131I trapping metastases with no 18FDG uptake and 18FDG trapping metastases with no 131I uptake. Five uptake types were differentiated. Alternating uptake was found in about 90% of the patients, which was nearly identical to the sensitivity of the combined 131I/18FDG investigation. In six patients with increasing human thyroglobulin levels, we found that 18FDG whole-body PET localized positive neck metastases of papillary thyroid carcinomas that were histologically confirmed after extirpation. CONCLUSION: Combination 18FDG and 131I whole-body imaging protocol enables detection of local recurrence or metastases on whole-body scans that are often not shown by other imaging methods. Biochemical grading of thyroid cancer may also be possible with this method: Tumors with remaining functional differentiation for hormone synthesis and iodine uptake have low glucose metabolism in more than 95%; tumors without this functional differentiation of 131I uptake show high, glucose metabolism. Fluorine-18-FDG uptake seems to be an indicator of poor functional differentiation, and possibly higher malignancy, in thyroid cancer.

[18FDG whole-body PET in differentiated thyroid carcinoma. Flipflop in uptake patterns of 18FDG and 131I]. / 18FDG-Ganzkörper-PET bei differenzierten Schilddrüsenkarzinomen. Flipflop im Speichermuster von 18FDG und 131J.

In 27 examinations of 24 patients with differentiated thyroid carcinoma an alternating pattern of metastases with either 131I- or FDG-uptake was found. In the follow-up of these patients this flip-flop pattern was seen in 89% (17/19) of patients with metastases and uptake of 131I or FDG as described here as uptake types 1 and 2 (type 1: FDG-positive and 131I-negative; type 2: FDG-negative and 131I-positive). In 4 patients a mixed type was observed (uptake type 3), i.e. a combination of metastases with uptake types 1 and 2 in the same patient. Metastases of papillary or follicular thyroid carcinoma without uptake of iodine have all been found to be FDG-positive in patients with an increase of thyroglobulin and with negative diagnostic results from other imaging modalities, and were histologically confirmed by surgery. False-negative or false-positive cases were not observed in this study. The FDG uptake showed an inverse proportionality to iodine uptake and to tumor differentiation. Increased glucose metabolism is a sign of higher malignancy.

Upward creep of the heart in exercise thallium 201 single photon emission tomography: clinical relevance and a simple correction method.

The upward creep of the heart during myocardial single photon emission tomography (SPET) acquisition has been reported as a frequent source of false-positive results. The aim of this study was to simplify the detection and correction of this upward creep and to estimate its clinical relevance during routine patient care. To recognize the upward heart motion a straight line was fitted to the upper and lower border of consecutively displayed tomographic projection images. In this way, vertical translation of at least 1 pixel in size could be detected easily. On the assumption of a slow but continuous upward motion a fast interpolation correction method was developed. From 100 consecutive, supine, ergometric exercise studies, 1, 2 or 3 pixels of upward creep were found in 16, 4 or 3 patients, respectively. It was found that an upward creep of at least 2 pixels (7/100 cases) led to evident, mostly antero-septal defects on quantitative bull's-eyes, whereas only upward creeps of 3 pixels or more (3/100 cases) produced false-positive diagnostic results. The simple correction method offered a sufficient compensation of image and/or bull's-eye artefacts. These clinical findings could be reproduced in a computer model. Thus, it can be stated that clinically significant upward creep of the heart during stress SPET acquisition is relatively rare; it may have been overestimated in the past, and its artificial effects can be corrected by a quick and simple algorithm.

Application of P-31 nuclear magnetic resonance spectroscopy to a new experimental kidney perfusion model using cadaveric porcine kidneys from slaughterhouse.

Larger NMR magnets with relatively high field strengths have become available recently, allowing the application of magnetic resonance spectroscopy (MRS) in larger mammalian organs. The aim of this study was to develop and test a new and simple kidney perfusion model from slaughterhouse swine using a new 4.7-tesla/40-cm diameter system, with the intention behind to provide a human-like mammalian experimental kidney perfusion model, and to avoid sensitive in vivo animal experiments on higher-developed mammalians, 35 pig kidneys obtained 10-15 min post mortem were studied to evaluate and define conditions for optimum metabolic preservation with the following perfusion protocols: (1) immediate plegia with cold Collins solution, 1-3 h cold storage, P-31 MRS; (2) immediate plegia, 1-3 h cold storage, blood reperfusion, P-31 MRS; (3) immediate blood reperfusion, plegia, 1-3 h cold storage, blood reperfusion, P-31 MRS; (4) immediate blood reperfusion, plegia, 24 h cold storage, blood reperfusion, P-31 MRS, P-31 MRS at 81 MHz with a double-tuned surface coil yielded the following results: [table: see text] Blood flow showed a weak correlation with beta-ATP/inorganic phosphate in protocols 3 and 4 of r = 0.64. Repeated reperfusion and ischemia experiments of this model allowed the on-line observation of the metabolic response of the energy phosphate pattern for several hours. In conclusion, slaughterhouse-harvested swine kidneys lend themselves to a simple, low-cost in vitro perfusion model, provided they are reperfused with arterial blood immediately after harvesting.(ABSTRACT TRUNCATED AT 250 WORDS)

Reproducibility of quantitative hexakis-2-methoxyisobutylisonitrile single photon emission tomography in stable coronary artery disease.

The quantification of myocardial perfusion abnormalities is necessary to allow comparison of repeated studies, especially in the evaluation of the success of medical, interventional or combined treatment in stable coronary artery disease or in evolving myocardial infarction. The purpose of this study was to assess inter-observer reproducibility of tomographic study processing using a semi-automatic quantitative programme. Technetium 99m hexakis-2-methoxyisobutylisonitrile (99mTc-Sestamibi) was chosen for tomographic imaging of repeated rest-stress studies in patients with stable coronary artery disease. The quantification was performed using a modification of the Cedars polar coding and comparison with the normal data base. The perfusion defects were quantified separately for each standard perfusion area [left anterior descending (LAD), right coronary (RCA) and left circumflex (LCX) arteries] and total area of hypoperfused myocardium. The inter-observer variability for 40 tomographic studies was accomplished. The defects were the largest in the LAD perfusion area (average 19.7% of the normalized LAD supply area) with an inter-observer correlation of 0.84 for this region. The greatest variability was found for the LCX region (r = 0.55) and is attributed to a small average perfusion defect (7.1%), only 18 studies having abnormal perfusion in this area. In total, an average 14.3% of the left ventricular myocardium was significantly hypoperfused, and the inter-observer correlation was 0.87. These results show good inter-observer reproducibility using semi-automatic quantitation of perfusion defects. Careful interpretation of smaller defects in the evaluation of treatment results is advised when repeated 99mTc-Sestamibi single photon emission tomography studies are processed by more than one observer.

[The effect of 3-dimensional data stabilization in radionuclide ventriculography on the statistical numerical error in the ejection fraction]. / Einfluss einer dreidimensionalen Datenstabilisierung in der Radionuklidventrikulographie auf den statistischen Zählfehler der Ejektionsfraktion.

The suitability of a 3-dimensional filter in diminishing the statistical noise of left ventricular volume curves without any systematical error in the left ventricular ejection fraction (EF) was investigated. The EF values were compared in 50 studies on 24 patients. There was no significant systematical difference between the EFs before and after filtering. The filter diminishes the statistical uncertainty of the EF by a factor of 0.47. Therefore, the method may possibly be employed in processing the left ventricular volume curves.

Hydrogen/fluorine retuning tomography. Applications to 1H image-guided volume-selective 19F spectroscopy and relaxometry of perfluorocarbon emulsions in tissue.

A hardware modification which permits the record of 19F images, spectra, and relaxation times with a 1H tomography bird-cager resonator is described. Changing the spectrometer frequency from 1H to 19F resonance and vice versa is possible without removing the object to be investigated. This hydrogen/fluorine retuning tomography (HYFY) technique permits studies of identical slices or volume elements with 1H as well as with 19F resonance. In particular, it is possible to localize volume elements on the basis of multislice proton images and then to investigate these volume elements with fluorine magnetic resonance by the aid of volume selection methods. For this purpose, pulse sequences for the localized and spectroscopically resolved determination of spin-lattice and transverse relaxation times have been developed. The applicability of the techniques has been demonstrated by the aid of phantom samples as well as with excised porcine organs which have been perfused with perfluorocarbon emulsions.

[Studies of myocardial metabolism using P-31-NMR spectroscopy and a simple heart perfusion model of slaughtered animals--an approach to avoiding in vivo animal experiments]. / Myokard-Stoffwechseluntersuchungen mit der P-31-NMR-Spektroskopie und einem einfachen Herz-Perfusionsmodell von Schlachttieren--ein Ansatz zur Vermeidung von In-vivo-Tierexperimenten.

In research cardiology large numbers of in vivo animal experiments, mostly with dogs or pigs, are necessary. It was the aim of this study to test a simple in vitro perfusion heart model from swine harvested in the slaughterhouse as a potential substitute for in vivo animal studies. 32 unselected hearts of slaughterhouse swine after 10 to 15 min of warm ischemia were subjected to reperfusion with warm oxygenized blood and were examined for mechanical recovery, which occurred in 56%, increasing to 95% if primarily using only hearts that were in relaxation. In 21 of selected relaxed heart models the energy phosphate pattern as an index of viability was measured by P-31 MRS on a 4.7 Tesla NMR tomograph in 37 experimental runs with the following perfusion protocols: 1) immediate cardioplegia with cold Bretschneider or Collins solution, transportation under cooling, MRS after approximately 1 h; 2) immediate cardioplegia, transportation, reperfusion with oxygenated warm blood, MRS; 3) immediate blood perfusion with genuine fresh arterial blood from the slaughterhouse, cold plegia perfusion, transportation, MRS; 4) immediate blood perfusion with transportation MRS; 4) immediate blood perfusion with genuinefresh arterial blood, cold plegia perfusion, transportation, reperfusion with oxygenated warm blood, MRS during reperfusion; 5) An experimental pig heart was made plegic in vivo and reperfused with oxygenated warm blood during MRS as reference.(ABSTRACT TRUNCATED AT 250 WORDS)

[Quantification of the myocardial scar with technetium-99m-isonitrile (MIBI) in emission computerized tomography (SPECT)--comparison with serial creatine kinase determinations and radionuclide ventriculography]. / Quantifizierung der Myokardnarbe mit Technetium-99m-Isonitril (MIBI) in der Emissionscomputertomographie (SPECT) Vergleich mit Kreatinkinase-Serienmessungen und der Radionuklidventrikulographie.

Estimation of the size of myocardial infarction is of major interest for clinical patient management and a simple and reliable method is still searched for. In this study the potential of the new myocardial perfusion tracer, Technetium-99m (Tc-99m) methoxy-isobutyl-isonitril (MIBI) combined with emission computertomography (SPECT), is tested vs. the standard procedures of serial plasma creatine kinase (CK) measurements and radionuclide ventriculography (RNV). In 10 patients with first myocardial infarction, integral values for CK were obtained during the acute phase. Following three weeks of uncomplicated recovery the patient was referred for both types of myocardial imaging within four days. 370 MBq Tc-99m-MIBI were injected with the patient supine and at rest. One hour later SPECT acquisition commenced. The reconstructed slices were rearranged to long and short axes slices, which served to calculate a functional "scar image" in polar coordinates. The color-coded areas of significantly reduced tracer uptake were expressed in percent of the total myocardial area. RNV was performed with the patient supine and at rest, the left anterior oblique angle being optimized for septum visualization. Infarct localizations were antero-apical (three), anterolateral (two), postero-lateral (one), and posterior (four).(ABSTRACT TRUNCATED AT 250 WORDS)

The contraction fraction (CF) in myocardial studies with technetium-99m-isonitrile (MIBI)--correlations with radionuclide ventriculography and infarct size measured by SPECT.

Criteria for the detection of coronary artery disease in nuclear cardiology include visualization of perfusion defects and functional impairment of contraction. The purpose of this study is to combine both methods in one procedure with the new myocardial perfusion tracer, 99mTc-methoxy-isobutyl-isonitril (MIBI), reducing time and radiation burden to the patient. Following an uncomplicated recovery, ten patients with first myocardial infarction participated in this study. Radionuclide ventriculography (RNV) was performed at rest and during exercise. Within 2-3 days, 370 MBq 99mTc-MIBI were injected and SPECT acquisition commenced 1 h later. Data processing included a scar image in polar coordinates. Areas of significantly reduced tracer uptake were expressed as a percentage of the total myocardial area. Directly following SPECT, resting and maximum exercise gated planar LAO images were recorded and the contraction was quantified. The concept of the contraction fraction (CF) rested on the end systolic change in count distribution: their increase in density and their centripetal concentration. For comparison, geometrical inner edge detection techniques were also applied. All algorithms for describing an EF equivalent were verified by computer simulations, showing a perfect correlation over a wide range of preset EFs. When applied to the patient studies only the non geometric methods revealed a good correlation with the ejection fraction (EF) obtained by RNV, and with the infarct size measured by SPECT.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization of enteral protein loss by 99m-technetium-albumin-scintigraphy.

Using 99mTc-Albumin scintigraphy in a patient with constrictive pericarditis and a highly positive Gordon test (35% albumin elimination in 5 days), it was possible to localize the protein loss in the small bowel for planning surgical treatment. Tc-HSA imaging is an easy method for qualitative investigation of protein losing enteropathy in the bowel. This technique is not as time consuming and cumbersome as the Gordon test and, in addition, allows the exact localization of protein loss.