Insulin resistance in liver cirrhosis. Positron-emission tomography scan analysis of skeletal muscle glucose metabolism.

BACKGROUND: Insulin resistance and glucose intolerance are a major feature of patients with liver cirrhosis. However, site and mechanism of insulin resistance in cirrhosis are unknown. We investigated insulin-induced glucose metabolism of skeletal muscle by positron-emission tomography to identify possible defects of muscle glucose metabolism in these patients. METHODS: Whole body glucose disposal and oxidation were determined by the combined use of the euglycemic-hyperinsulinemic clamp technique (insulin infusion rate: 1 mU/kg body wt per min) and indirect calorimetry in seven patients with biopsy-proven liver cirrhosis (Child: 1A, 5B, and 1C) and five healthy volunteers. Muscle glucose uptake of the thighs was measured simultaneously by dynamic [18F]fluorodeoxyglucose positron-emission tomography scan. RESULTS: Both whole body and nonoxidative glucose disposal were significantly reduced in patients with liver cirrhosis (by 48%, P < 0.001, and 79%, P < 0.0001, respectively), whereas glucose oxidation and the increase in plasma lactate were normal. Concomitantly, skeletal muscle glucose uptake was reduced by 69% in liver cirrhosis (P < 0.003) and explained 55 or 92% of whole body glucose disposal in cirrhotics and controls, respectively. Analysis of kinetic constants using a three-compartment model further indicated reduced glucose transport (P < 0.05) but unchanged phosphorylation of glucose in patients with liver cirrhosis. CONCLUSIONS: Patients with liver cirrhosis show significant insulin resistance that is characterized by both decreased glucose transport and decreased nonoxidative glucose metabolism in skeletal muscle.

Positron emission tomography in neuropsychiatric lupus erythematosus.

We performed positron emission tomography (PET) using 18F-labeled 2-F-2-deoxyglucose in 13 patients with systemic lupus erythematosus (SLE). Ten of them had clinical signs of central nervous system involvement (NP-SLE). All patients with neurologic symptoms showed pathologic changes on PET, always in accordance with the clinical state. Three patients without neuropsychiatric manifestations had normal PETs. Computed tomography of the brain and magnetic resonance imaging proved to be less sensitive to both presence and localization of CNS lesions. We conclude that the combination of PET and MRI constitutes the most useful diagnostic procedure for NP-SLE.

Risk factors in follicular thyroid carcinomas. A retrospective follow-up study covering a 14-year period with emphasis on morphological findings.

One hundred sixty-seven patients with follicular carcinomas and 88 with atypical adenomas of the thyroid have been followed up for up to 14 years. The influence of tumor invasiveness; tumor extent at time of presentation, including degree of metastatic spread; and age of patients have been evaluated by determining the rate at which distant metastases or deaths occurred during the later course of disease after surgery had been performed. The degree of tumor invasiveness has been found to be of great prognostic weight. Atypical adenomas did not show recurrences during the time of observation. The most important diagnostic distinction made with regard to prognosis was found to be between minimally invasive (encapsulated) and extensively invasive carcinomas.

Cerebral dynamics of N-isopropyl-(123I)p-iodoamphetamine.

Temporal changes in the distribution of N-isopropyl-(123I)p-iodoamphetamine (IMP) within the brain are measured with serial tomographic imaging. In the cerebellum there is a decrease in activity of 42% from the early [15-45 min postinjection (p.i.)] to the late (210-240 min p.i.) scan, while in the cortex the decrease is 18%, and in the basal ganglia there is no decrease within this time. In brain tumors there was no IMP uptake in the early as well as in the late scans, regardless of tumor type, perfusion rate, or blood-brain barrier dysfunction. In 11 of 43 patients with a cerebral infarction a real increase of 123I activity (mean +21%) was seen in the late images. This "filling in" phenomena might be useful in selecting patients for bypass surgery. In these patients the diaschisis cerebelli, seen in the early scans, disappeared in the late images. The regional distribution of IMP changes with time; spatial ratios might be blurred by temporal changes. High-flow areas such as visio-auditory centers can be delineated clearly after stimulation in fast early scans; in these areas the pharmacokinetics of 123I are different from other cortex regions. To get the full information from the IMP brain uptake, both spatial and temporal variation must be measured.

Accurate local blood flow measurements with dynamic PET: fast determination of input function delay and dispersion by multilinear minimization.

Accurate determination of local blood flow in tissue using the Kety-Schmidt one-compartment model for freely diffusible tracers requires knowledge of the true arterial input function in tissue. Because measured input functions are usually delayed and dispersed with respect to true influx, a correction of the experimental input function is necessary. We describe a technique that uses a fast multilinear least-squares minimization procedure to determine simultaneously the dispersion, the blood flow and the partition coefficient as a function of delay. In this approach, a few multilinear fits are sufficient to determine the complete set of parameters necessary to describe the data. Because of the high speed of the procedure, dispersion effects may be taken into account on a pixel-by-pixel basis in calculating parametric images of blood flow and partition coefficient. The described procedure has been used at our institute for about 1 yr in more than 160 investigations and has proven well suited for routine use in a clinical environment.

A kinetic model for cardiac PET with [1-carbon-11]-acetate.

UNLABELLED: Carbon-11-labeled acetate is a unique tracer for noninvasive assessment of myocardial oxidative metabolism with PET. Because adequate kinetic models have been missing, data evaluation in the past was performed mostly with phenomenological approaches such as mono- or biexponential fitting which cannot account for the influence of finite input duration and blood volume encountered in noninvasive PET investigations. METHODS: To investigate to what extent the current data evaluation schemes are justified, we developed a comprehensive model of [1-11C]-acetate kinetics in the myocardium which incorporates five tissue compartments: free acetate, activated acetate, CO2 precursors, amino acids and CO2. We derived the analytical solution of the model equations which is used for simulations and data fitting. RESULTS: The five-compartment model can reproduce in detail known experimental data. The resulting values of the eight model parameters compare favorably with existing biochemical facts. We have established the relation between parameters of the detailed model and one- and two-compartment models used for the evaluation of PET investigations. CONCLUSION: The kinetics of [1-11C]-acetate are adequately described by a five-compartment model. One- and two-compartment models are sufficient for simultaneous quantitative assessment of myocardial oxidative metabolism and perfusion with [1-11C]-acetate and PET.

A compartmental model for alveolar clearance of pertechnegas.

UNLABELLED: The washout of an inhaled water soluble radiotracer from the lungs is a measure of alveolar integrity. Data evaluation of 99mTc-DTPA studies were previously performed mainly with monoexponential fitting with or without background subtraction. The introduction of 99mTc-pertechnegas for the assessment of alveolar permeability necessitates the investigation of adequate data evaluation schemes for this radiotracer. METHODS: We developed a three-compartmental model to describe 99mTc-pertechnegas kinetics after inhalation. Monoexponential fitting of the first 5 min was investigated as simplification for clinical use. Different background corrections based on blood samples or representative regions of interest were compared. RESULTS: Correction of intra- and extravascular background by subtraction of calibrated curves, which are derived from blood or background areas, resulted in monoexponential washout curves. Clearance rates based on the three-compartmental model were nearly the same as those derived from a monoexponential fit after blood-activity subtraction (r = 0.96). A monoexponential analysis of the first 5 min without any background correction correlates well with the first component of the biexponential analysis (r = 0.97). CONCLUSION: A dynamic study of more than 45 min allows quantitative determination of the transfer rate of 99mTc-pertechnegas from the alveoli into the blood using compartmental analysis. A simplified monoexponential analysis of the first 5 min allows assessment of lung clearance without any background correction.

Oxygen-15-water PET assessment of muscular blood flow in peripheral vascular disease.

UNLABELLED: To assess quantitatively regional nutritive muscular blood flow in patients with peripheral vascular disease (PVD), we evaluated the utility of PET with 15O-water. METHODS: Eight healthy volunteers and 16 patients with angiographically proven PVD were studied. Regional blood flow of the calf was measured with 15O-water PET during rest, after intra-arterial infusion of prostaglandin E1 and during ergometry. The studies were quantified using a one tissue compartment model. RESULTS: Normalized mean tracer uptake from 15-60 sec correlated closely (r = 0.98) with absolute blood flow. Scan times longer than 90 sec were required to determine blood flow reliably. The flow values were overestimated by 2% if arterial blood volume was neglected or if the input function delay was corrected globally for parametric imaging. Mean blood flow of calf muscles at rest did not differ significantly between patients (0.017 +/- 0.006 ml/min/ml) and control subjects (0.018 +/- 0.010 ml/min/ml). In PVD patients, blood flow increased by 100% after intra-arterial infusion of PGE1 in the respective leg. In the control subjects, average flow increased by a factor of six during exercise. The increase was more pronounced in the extensor muscles (0.182 +/- 0.031 ml/min/ml) than in flexor muscles (0.121 +/- 0.045 ml/min/ml). Due to the specific type of ergometry, superficial flexors exhibited higher flow values than the profound ones. CONCLUSION: PET with 15O-water enables reliable determination of regional nutritive skeletal muscle blood flow for research and clinical applications in patients with PVD.

Dopamine transporter binding in Gilles de la Tourette syndrome.

Preliminary studies in patients with Gilles de la Tourette syndrome (TS) provided evidence of presynaptic dopaminergic dysfunction, demonstrating increased reuptake sites. Therefore we investigated striatal dopamine transporter binding in 12 TS patients and 9 control subjects using single photon emission computed tomography and 123I-labeled 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane. In TS patients we found significantly higher relative striatal activity ratios (mean +/- SD 12.33 +/- 3.58) than in controls (9.36 +/- 1.35, P< 0.05). Only five patients, however, showed striatum/occipital cortex ratios more than 2 SD above the normal means. Seven patients had activity ratios within the average ratio of the control group plus 2 SD. Regarding the relationship between clinical parameters and striatum/occipital cortex ratios, we found an association between binding ratios and "self-injurious behavior" and "lack of impulse control." This study corroborates previous data suggesting an involvement of the dopaminergic system in TS pathology. Our results demonstrate that an increase in dopamine transporter capacity is a possible but not a necessary alteration, and which appears more likely when self-injurious behavior and lack of impulse control are associated.

[Indications for sonography in the investigation of the thyroid gland (author's transl)]. / Zur Indikation der Sonographie innerhalb der Schilddrüsendiagnostik.

The indications for using sonography in the investigation of the thyroid gland are discussed. Correlation of echo patterns and thyroid disease has shown that sonography deserves a place in the diagnosis of thyroid disease in the same way as the classical methods, such as clinical examination, scintigraphy, laboratory investigations and aspiration biopsy. The indications for sonography, which are illustrated by a number of examples, include: 1) when scintigraphy cannot be used, 2) pre-operative demonstration, 3) disagreement between clinical findings and the scintigram, 4) diagnosis of cysts, 5)suspicion of thyroiditis.

[NMR and CT studies in acute and late-stage cerebral infarct]. / MR- und CT-Untersuchungen bei Hirninfarkten im Akut- und Spätstadium.

MR offers an additional non-invasive means for the investigation of cerebro-vascular disease. This new digital imaging method competes with CT. Twenty-four patients with cerebral infarcts were examined by CT and MR; of these, 12 were in the acute stage of necrosis and resorption, and 12 were examined after six weeks following the formation of cysts and glial scars. Because of the increased relaxation time of T1 and T2, there is a large signal difference between infarcted and normal brain. Consequently, cerebral infarcts can be clearly recognised during the first 24 hours. MR also has advantages in demonstrating infarcts in the pons and medulla and if one wishes to avoid contrast enhancement during CT. Problems may arise in differentiating fresh infarcts from haemorrhage and from gliomas. At the present time, the length of the procedure and its high cost justify MR in exceptional circumstances only.

[Scintigraphic image of bile reflux following gastric and intestinal surgery]. / Szintigraphische Darstellung des Gallenrefluxes nach Magen- und Darmoperationen.

Bile reflux may occur after a variety of reconstructive procedures in the gastro-intestinal tract and biliary system. The present paper deals with reflux into the duodenum, jejunum, stomach, oesophagus and into blind loops. The demonstration of reflux by 99mTc labelled IDA acid derivatives, and a possible quantitative approach, are discussed. The advantages of an isotope method are: 1. Direct demonstration of bile reflux without any intervention in the physiological process and with little trouble to the patient, 2. The ability to use the method for various reconstructive procedures and 3. The additional information obtained which may help in the differential diagnosis of blind loops, biliary obstructions, cholecystitis or liver metastases if there has been a gastrectomy for a malignant tumour. In combination with a second administration of a radio-isotope tracer, one may be able to demonstrate abnormalities in the motility of the stomach or gut, or pyloric stenosis or gastro-oesophageal reflux.

[Hepatobiliary sequential-scintigraphy--progress in the evaluation of postcholecystectomy complains (author's transl)]. / Hepatobiliäre Sequenzszintigraphie--Fortschritte in der Abklärung von Rest- und Nachbeschwerden Cholezystektomierter.

The hepatobiliary sequential-scintigraphy is a nuclear diagnostic procedure useful in assessing the function of liver and biliary system. 40 patients with and 20 patients without complains following cholecystectomy were examined. The value of this method in establishing biliary causes for such complains is demonstrated by typical cases. Simplicity and safety in application as well as diagnostic sensitivity should place the method in the first place evaluating postcholecystectomy complains. Succeeding indirect and direct radiologic techniques then may be used systematically with benefit for the patient and physician. Results indicate, that the procedure will be essential as well in evaluation as in analysis of nature and frequency of such complains by its superior presentation of intrahepatic bilestasis and functional mechanisms of the biliary system including the sphincter of Oddi.

[Dynamic reflux scintimetry for quantifying gastroesophageal reflux in patients with prolonged esophageal transit]. / Die dynamische Refluxszintimetrie zur Quantifizierung des gastroösophagealen Refluxes bei Patienten mit verlängertem ösophagealen Transit.

A combination of a radionuclide transit test and a dynamic gastroesophageal scan was evaluated in normal volunteers, in patients with achalasia treated by pneumatic dilatation (n = 34) or Heller myotomy (n = 21). Interpretation of 31 of 57 examinations done with usual scintiscan was not possible because of too high esophageal tracer retention. Only one case could not be interpreted with the modified technique. Gastroesophageal reflux was detected and quantified in this manner in 8 patients, 6 more than with the usual scintiscan. 7 of these 8 patients have had Heller procedure, 1 patient even combined with fundoplasty.

[Demonstration of postgastrectomy bile reflux by hepatobiliary sequential scintigraphy]. / Nachweis von Gallereflux nach Gastrektomie mit der hepatobiliären Sequenzszintigraphie (HBSS).

After gastrectomy and jejunal interposition by the Longmire technique, symptoms due to alkaline reflux oesophagitis may occur, which are caused by duodeno-jejunal and jejuno-oesophageal bile reflux. Twenty-seven patients who had gastrectomies performed for malignant tumours one to three years previously were examined by hepatobiliary sequential scintigraphy in order to see whether this is able to demonstrate bile reflux. In addition to endoscopies, biopsies and radiological examinations, 45 sequential scintigrams were carried out. Agreement of results during routine use was investigated for five observers. There were considerable variations in results amongst different observers. Nevertheless, in four out of the five observers, there was a significant correlation with the clinical findings (p less than 0.05). Only by using functional scintigraphy with digital data recording is it possible to demonstrate or exclude bile reflux with any degree of certainty. Eight out of twelve patients with marked symptoms, and four out of 28 without symptoms showed reflux into the interposed segment (correlation 0.7, p greater than 0.05). Patients with symptoms showed a high incidence of oesophagitis by the above-mentioned methods (correlation (0.52, p greater than 0.05). Correlation between the results of barium meals and clinical findings was considerably less (0.25) and was not significant. Sequential scintigraphy is therefore better for clarifying reflux symptoms than radiological examination or endoscopy and biopsy.

[11C-methionine PET, IMP-SPECT, CT and MRI in brain tumors]. / 11C-Methionin-PET, IMP-SPECT, CT und MRI bei Hirntumoren.

11C-labelled L-methionine uptake was measured in 7 patients with brain tumours prior to surgery, and in 2 patients with infarction, using PET. The strongest uptake occurred in tumours with a high grade of malignancy (astrocytoma IV: Tumour/Non-Tumour T/NT = 2.6) while low-grade tumours accumulated less activity (astrocytoma II: T/NT = 1.4). Conventional 99mTc DTPA scans revealed a damage of blood brain barrier (BBB) in 4 patients (2 infarctions) with no or only slight 11C-methionine accumulation, while one patient with negative 99mTc-scan and negative CT accumulated methionine in the tumour region (astrocytoma II). PET, MRI, and CT are complementary with regard to extent of tumour tissue, necrotic areas and oedema. None of the brain tumours or infarcted regions took up IMP (123I amphetamine). The investigated regions showed definite uptake defects ranging from 10-50% if compared with the contralateral side. In view of the chemical pathway of methionine it is concluded that the uptake reflects metabolic activity in brain tumour tissue rather than a diffuse uptake due to BBB damage.

[Amino acid uptake in brain tumors using positron emission tomography as an indicator for evaluating metabolic activity and malignancy]. / Die Aufnahme von Aminosäuren in Hirntumoren mit der Positronen-Emissionstomographie als Indikator für die Beurteilung von Stoffwechselaktivität und Malignität.

Diagnosis and post-therapeutic follow-up of tumour patients necessitates morphological and particularly functional imaging methods. For the latter approach positron emission tomography has proven a valid tool for the measurement of perfusion, of energy consumption parameters such as oxygen extraction, glucose metabolism and amino acid uptake. However, neither perfusion nor energy consumption parameters have yielded unambiguous information on the clinical status of various tumours in respect of their malignancy and their growth status. It is shown in this paper that amino acid uptake seems to be a valid measure for the functional activity of tumour tissue for a broad range of neoplasms. The uptake of 11C-L-Methionine was measured in 33 patients having various brain tumours, and was compared with 6 patients who had an infarction, and with 8 patients suffering from arachnoidal cysts. The amino acid uptake correlated well with the histological grading of the tumours and the clinical status of the patient. The uptake was well differentiated against metabolically inactive lesions. Parallel investigations on the uptake mechanisms of amino acids in an animal model have shown that transport phenomena regulate the uptake rather than protein synthesis rates. However, protein synthesis may nevertheless exercise a control function on the transport process.

[Quantitative measurements of regional extra-vascular lung water in dogs using positron emission tomography]. / Quantitative Messung des regionalen extravaskulären Lungenwassers bei Hunden mit der Positronen-Emissionstomographie.

A new method for quantifying regional variations in extravascular lung water (rELW) has been developed. The positron source 15O (T1/2 = 2.0 min.) was provided as H215O 'on line' by constant intravenous injection. Tomographic images (PET) of the water distribution were obtained during equilibrium. The distribution of blood volume was obtained by marking erythrocytes (carboxyhaemoglobin) using a bolus inhalation [C-11)-CO; T1/2 = 20.4 min). Absorption is calculated from transmission tomography. The rELW is defined as: total lung water minus intravascular space. The method was carried out in five intubated and anaesthetised dogs before and after induction of pulmonary oedema with oleic acid (0.06 ml./kg.). Mean ELW (PET) rose from 0.13 +/- 0.02 g./cm.3 to 0.24 +/- 0.04 g./cm.3. There was good correlation with a simultaneously performed thermo-dye method (7.1 +/- 1.3 ml./kg. KG to 13.3 +/- 1.9 ml./kg. KG; r = 0.94). Gravimetric estimations resulted in 13.7 +/- 2.6 ml./kg. KG. The development and distribution of the pulmonary oedema was non-homogeneous and varied regionally.

[Is a dosage calculation for radio-iodine therapy possible?]. / Ist eine Dosisberechnung für die Radiojodtherapie möglich

When trying a single-dose 131I therapy in thyrotoxic patients a dose calculation must be done to avoid an overtreatment raising the risk of posttherapeutic hypothyroidism. The calculation is based on the diagnostic 131I uptake, the thyroid weight, and the effective intrathyroidal halflife of the diagnostic 131I dose. In 46 thyrotoxic patients the radiation dose was calculated with 7000 R for small and 10 000 R for large (50--100 g) glands using the formula of Billion. Iodine-131 was given in a single dose. Therapeutic dose uptake was measured every day and the effective T 1/2 calculated using a least squares computer fitting to an monoexponential decrease. The radiation dose was then recalculated using the same formula. Small glands received 10 700 +/- 4300 R (SEM 1008 R) instead of calculated 7000 R; large glands 8600 +/- 4100 R (SEM 860) instead of 10 000 R. There was a significant correlation: the smaller the gland the higher the radiation dose. The smallest glands received 12 000 to 16 000 R. There might be such a great difference between calculated and received radiation dose than an individual prediction will be impossible. In our patients a careful calculation for the single-dose treatment was done; nevertheless in some cases an overtreatment of more than 100% was seen. A comparison of responding or overresponding to therapy with the radiation dose is only reliable using individual dosimetry with the therapeutic 131I dose.

[Determination of renal clearance with only a single access for injection and blood extraction]. / Bestimmung der renalen Clearance mit nur einem Zugang für Injektion und Blutentnahme.

An injection technique was developed to administer radioactivity to children and adults and to withdraw plasma samples through the same venous line. The error in clearance estimation due to "contamination" was smaller than that caused by the timing of blood sampling or the type of algorithm used for clearance calculation.