Noninvasive quantification of hepatic steatosis inrats using 3.0 T 1H‐magnetic resonance spectroscopy

Purpose:

To assess the accuracy of noninvasive 3.0 T ¹H‐magnetic resonance spectroscopy (¹H‐MRS) in an experimental steatosis model for the discrimination of clinically relevant macrovesicular steatosis degrees and to evaluate three different ¹H‐MR spectrum‐based fat quantification methods.

Materials and Methods:

Steatosis was induced in rats by a methionine/choline‐deficient diet for 0–5 weeks. ¹H‐MRS measurements of hepatic fat content were compared with histopathological and biochemical steatosis degree. In ¹H‐MR spectra, areas under the curve (AUC) of fat (1.3 ppm), water (4.7 ppm), total fat (0.5–5.3 ppm), and total spectrum peaks (0.5–5.3 ppm) were determined and hepatic fat content calculated as follows: [AUC_{total fat peaks}/AUC_{total peaks}], [AUC_fat/AUC_fat + (AUC_water/0.7)], and [AUC_fat/AUC_water].

Results:

A significant correlation was found between ¹H‐MRS and macrovesicular steatosis (r = 0.932, P < 0.0001) and between ¹H‐MRS and total fatty acids (r = 0.935, P < 0.0001). ¹H‐MRS accurately distinguished mild from moderate and moderate from severe steatosis. Calculations using [AUC_fat/AUC_water] ratio in severe steatotic livers resulted in higher hepatic fat percentages as compared to the other methods due to a decrease in hepatic water content.

Conclusion:

¹H‐MRS quantification of hepatic fat content showed high correlations with histological and biochemical steatosis determination in an experimental steatosis rat model and accurately discriminated between clinically relevant steatosis degrees. These results encourage further application of ¹H‐MRS in patients for accurate steatosis assessment. J. Magn. Reson. Imaging 2010;32:148–154. © 2010 Wiley‐Liss, Inc.     

A 31P NMR study of the GI tract: effect of fructose loading and measurement of transverse relaxation times

The effect of fructose loading on high-energy phosphates in the jejunum, ileum, and large intestine of rats was studied using 31P NMR. Following fructose loading, an increase in the intensity of the PME resonance was observed in the jejunum, indicating an accumulation of fructose-1-phosphate. There were no significant changes in ATP or Pi. This demonstrates that the activity of fructokinase in the jejunum can be monitored by 31P NMR. Fructose loading had no detectable effect on metabolite levels in the ileum and large intestine. Resolution of intestinal spectra was poor due to unusually large linewidths and the presence of broad underlying signals. To study the mechanism of line broadening, the T2's of the phosphorus resonances were measured using a solenoidal coil. The T2's of the ATP, Pi, PME, and PCr resonances were much longer than the T2's, suggesting that the linewidths of these resonances are primarily due to susceptibility gradients and/or compartmentation of metabolites. Other signals, particularly in the PDE region, were homogeneously broadened and had very short T2's. Spin echoes obtained with evolution times of 1 to 4 ms suppressed these broad components, with little loss of intensity in the inhomogeneously broadened resonances; as a result, resolution was improved.     

Quantifying hepatic glycogen synthesis by direct and indirect pathways in rats under normal ad libitum feeding conditions

Hepatic glycogen synthesis from intact hexose (direct pathway) relative to that from gluconeogenic precursors (indirect pathway) was quantified in ad libitum‐fed rats. Following ²H₂O administration and overnight feeding, the livers were removed and glycogen ²H‐enrichment was measured by ²H NMR. Six controls and six rats rendered hyperglycemic by streptozotocin (STZ; fasting blood glucose = 385 ± 31 mg/dl) were studied. The indirect pathway contribution, estimated as glycogen hydrogen 5 relative to hydrogen 2 enrichment, was 54% ± 4% for control rats—similar to values from healthy, meal‐fed humans. In STZ‐treated rats, the indirect pathway contribution was significantly higher (68% ± 4%, P < 0.05 vs. controls), similar to that of Type 1 diabetic (T1D) patients. In conclusion, sources of hepatic glycogen synthesis in rats during ad libitum nocturnal feeding were quantified by analysis of glycogen enrichment from ²H₂O. STZ caused alterations resembling the pathophysiology of hepatic glycogen synthesis in T1D patients. Magn Reson Med 61:1–5, 2009. © 2008 Wiley‐Liss, Inc.     

Evaluation of hepatic fibrosis with portal pressure gradient in rats

MRI has the potential of providing a noninvasive assessment of liver pathology. This work introduces a portal pressure gradient (PPG) model derived from fluid mechanics, where the PPG is proportional to the average velocity and inversely proportional to the vessel area in the upper part of portal vein. Using a phase‐contrast spoiled gradient echo sequence, the PPG model was verified in a phantom study and was tested in an animal study using 35 rats with various degrees of hepatic fibrosis induced by carbon tetrachloride (CCl₄). Histological examination was conducted to determine the severity of hepatic fibrosis. The fibrosis score monotonically increased with the duration of CCl₄ treatment. The PPG was highly correlated with nonzero fibrosis scores (r² = 0.90, P < 0.05). There was a significant difference between control and cirrhosis groups (P < 0.0006, α < 0.0018). The difference between control and fibrosis (noncirrhosis) groups (P < 0.002, α < 0.006) was also significant. Without the administration of any contrast agent, the MRI‐PPG approach shows promise as a noninvasive means of evaluating liver fibrosis. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Phosphorus-31 magnetic resonance spectroscopy of experimentally induced arthritis in rats

Phosphorus-31 magnetic resonance spectroscopy (MRS) of the hind paws of rats was performed at 1.5 Tesla before and during the course of an experimentally-induced inflammatory arthritis. Arthritis was induced by daily subcutaneous administration of 6-sulfanilamidoindazole, an antibacterial sulfa known to produce an acute, self-limited arthritis and periarthritis in the hind paws of rats.Phosphorus-31 spectra obtained after the development of clinical arthritis showed a significant (p<0.01) increase in the intensity of a group of resonances occurring downfiled from phosphocreatine as compared to spectra obtained before treatment. In all rats, this increase correlated well with histological evidence of inflammation as well as with the degree of inflammation judged clinically (r=0.89, p<0.001), and was present before roentgenographic evidence of bony involvement. The use of ³¹P MRS may permit evaluation of the severity of an inflammatory arthritis with greater accuracy than the bony changes definable by plain roentgenograms.This article is the award-winning Resident Paper of the International Skeletal Society for the year 1986. Support for its presentation at the annual meeting was contributed by the Department of Radiology of the University of British Columbia     

Quantification of hepatic steatosis with MRI: The effects of accurate fat spectral modeling

Purpose

To develop a chemical‐shift–based imaging method for fat quantification that accounts for the complex spectrum of fat, and to compare this method with MR spectroscopy (MRS). Quantitative noninvasive biomarkers of hepatic steatosis are urgently needed for the diagnosis and management of nonalcoholic fatty liver disease (NAFLD).

Materials and Methods

Hepatic steatosis was measured with “fat‐fraction” images in 31 patients using a multiecho chemical‐shift–based water‐fat separation method at 1.5T. Fat‐fraction images were reconstructed using a conventional signal model that considers fat as a single peak at –210 Hz relative to water (“single peak” reconstruction). Fat‐fraction images were also reconstructed from the same source images using two methods that account for the complex spectrum of fat; precalibrated and self‐calibrated “multipeak” reconstruction. Single‐voxel MRS that was coregistered with imaging was performed for comparison.

Results

Imaging and MRS demonstrated excellent correlation with single peak reconstruction (r² = 0.91), precalibrated multipeak reconstruction (r² = 0.94), and self‐calibrated multipeak reconstruction (r² = 0.91). However, precalibrated multipeak reconstruction demonstrated the best agreement with MRS, with a slope statistically equivalent to 1 (0.96 ± 0.04; P = 0.4), compared to self‐calibrated multipeak reconstruction (0.83 ± 0.05, P = 0.001) and single‐peak reconstruction (0.67 ± 0.04, P < 0.001).

Conclusion

Accurate spectral modeling is necessary for accurate quantification of hepatic steatosis with MRI. J. Magn. Reson. Imaging 2009;29:1332–1339. © 2009 Wiley‐Liss, Inc.     

Metabolic changes in the rat brain after acute and chronic ethanol intoxication: A 31P NMR spectroscopy study

In this work, ³¹P phosphorus NMR (³¹P NMR) studies of the brain have been conducted in rats acutely and chronically intoxicated with ethanol. In both groups, changes in levels of high-energy phosphates were observed: increase of phosphocreatinine (PCr)/β AaTP and PCr/inorganic phosphate (P_i) in acute and long-term ethanol exposure, and decrease of P_iβ ATP after acute ethanol administration. These changes in high-energy phosphates, indicative of a reduction of adenosine triphosphate (ATP) and PCr consumption (PCr+ ADP + H⁺ ATP + Cr; ATP ADP + P_i), suggest a reduction of cerebral metabolism both in acute and chronic ethanol exposure. In addition, in the group of rats chronically intoxicated with ethanol, there were variations in phosphodiester peak intensities (decrease of phosphomonoester (PME)/phosphodiester (PDE), increase of PDE/β ATP), suggesting increased breakdown of membrane phospholipids. These changes could provide a metabolic explanation for the development of cerebral atrophy in chronic alcoholism.     

Fructose 3-phosphate and 5-phosphoribosyl-1-pyrophosphate formation in perhsed human erythrocytes: 31P NMR studies

³¹P NMR was used to study the formation of fructose 3-phos-phate (F3P) and 5-phosphoribosyl-1-pyrophosphate (PRPP) in perfused human erythrocytes, in the presence of 10 different combinations and concentrations of glucose, inosine, pyru-vate, fructose, and inorganic phosphate (P_i). (1) The cells were immobilized in alginate-coated agarose threads and perfused with a medium containing fructose, and the level of F3P increased continuously over more than 10 h. The net rate of F3P formation was independent of the concentration of 2,3-bis-phosphoglycerate (2,3-DPG) present in the cells. (2) PRPP was formed in high concentrations, relative to normal, in immobilized cells when they were perfused with a medium containing P_i at a low pH (6.6). (3) The 2,3-DPG level decreased simultaneously when the sample was perfused with a medium containing fructose, but without inosine or pyruvate. The measured intracellular pH and free Mg²⁺ concentration were constant in these experiments. (4) The experiments confirmed the presence of fructose-3-phosphokinase (E.C. 2.7.1.-) and ribose-phosphate pyrophosphokinase (E.C. 2.7.6.1) activity in the human erythrocytes and that the biosynthetic pathways are active in immobilized cells at 37°C. (5) The rates of accumulation of 2,3-DPG and phosphomonoesters (PME) appeared to be strongly correlated.     

In Vitro and in Vivo 13C and 31P NMR analyses of phosphocholine metabolism in rat glioma cells

In ivivo magnetic resonance spectroscopy (MRS) has revealed that phsophomonoesters (PME) such as phosphocholine (PCho) and phosphoethanolamine (PEth) are elevated in tumalrs and rapidly proliferating tissues. The regulation of PME levels and their relationship to proliferation are not well known. In the present study, we investigated the regulation of PCho and PEth levels in rat glioma cells grown in vivo and in vitro using ³¹P and ¹³C MRS. However, the ability of cells to produce choline endogenously is variable. To fully understand regulation of PCho levels, it is necessary to characterize the activity of the endogenous pathway, if it exists. This was first investigated by following the metabolic fate of ¹³C-labeled methionine of 9L glioma tumors in vivo. Our results indicate that there is a significant amount of de novo choline synthesis in ivivo. However, similar experiments performed in virro using cells cultured in bioreactors indicated that glioma cells themselves are unable to synthesize choline de novo, suggesting that the in vivo results were due to the involvement of extra-tunnoral organs, e.g., liver. Further in vitro experiments demonstrated that the uptake and phosphorylation of physiologically relevant concentrations of exogenous choline is very active in these systems. Thus, it appears that the exogenous pathway for PCho biosynthesis predominates and regulates PCho levels in glioma cells. Our results also demonstrate that PCho levels are lowest, and PEth levels are highest, in non-proliferating cells. These observations indicate that there is a decrease in the biosynthesis of PCho concomitant with a redulction in culture growth. The source of the increased PEth is, as yet, undefined.     

In Vivo 31P NMR measurement of glucose-6-phosphate in the rat muscle after exercise

Comparison of ³¹P NMR spectra of the rat gastrocnemius, obtained in vivo and from PCA extracts, after electrically induced contractions, demonstrates that glucose-6-phosphate (G6P) is the major metabolite in the low-field part of the PME spectral region. In vivo ³¹P NMR can thus be used to measure the muscle G6P concentration after exercise.     

Biodistribution of rhenium-188 Lipiodol infused via the hepatic artery of rats with hepatic tumours

The purpose of this study was to analyse the biodistribution of rhenium-188 Lipiodol in rats with hepatic tumours following intrahepatic arterial injection to assess the potential of¹⁸⁸Re-Lipiodol as a radiopharmaceutical for the treatment of hepatic tumours in humans. Twelve male rats with hepatic tumours were killed at 1 h, 24 h and 48 h after injection of approximately 7.4 MBq of¹⁸⁸Re-Lipiodol via the hepatic artery. Samples of various organs were obtained and counted to calculate the tissue concentration. Radioactivity in the hepatic tumours was very high throughout this study, with a biological half-life of 122.9 h. Radioactivity in the normal liver tissue was also high, but was significantly lower than in the tumour. The biological half-life in the normal liver tissue was 31.7 h. The ratio of tumour concentration to the normal liver tissue concentration was 5.15 at 1 h and rose to 7.7 at 24 h and 10.84 at 48 h. The level of radioactivity in the lung was high at 1 h, and declined rapidly over time. The level of radioactivity in the kidney was moderate throughout the study. The radiation concentrations in muscle, spleen, testis, bone and whole blood were insignificant. We conclude that¹⁸⁸Re-Lipiodol should be considered as a potential radiopharmaceutical for the intra-arterial treatment of hepatic tumours.     

Selection of the most powerful predictors for the evaluation of hepatic steatosis grade: an experimental study

Purpose

To select the most powerful predictors for the evaluation of hepatic steatosis grade.

Methods and materials

Forty-five healthy New Zealand rabbits were randomly divided into one normal control group and three experimental groups. Hepatic steatosis models were established by feeding a high-fat, high-sugar diet and drinking water containing 5% ethanol. Twenty-two variable indexes were measured using general observation, biochemical examination, ultrasonography, computed tomography (CT), and proton magnetic resonance spectroscopy (MRS). Univariate analysis, correlation analysis, and stepwise regression analysis were used to make the selection of the most powerful predictors. ROC analysis was used to compare the diagnostic efficacy of single index with combined index (Y) expressed by a regression equation.

Results

Based on statistical analysis, there were 12 variable indexes with significant differences among groups, which correlated with hepatic steatosis grade: liver weight, hepatic index, liver CT value, liver-to-muscle attenuation ratio, ¹H MRS fat peak value, fat peak area, fat-to-water peak area ratio, fat percentage, ultrasound attenuation coefficient, serum aspartate aminotransferase, total cholesterol (TC) and triglycerides. Among them hepatic index, liver CT value and serum TC were selected as the most powerful predictors for hepatic steatosis grade with correlation coefficients of 0.709, −0.764, and 0.886, respectively. The regression equation was: Y = 1.975 + 3.906 × 10⁻²X₁ + 0.369X₂ − 2.84 × 10⁻²X₃, where Y = hepatic steatosis grade, X₁ = TC, X₂ = hepatic index, and X₃ = liver CT value. ROC analysis displayed PPV, NPV, curve area of combined index (Y) were superior to simple index (hepatic index, liver CT value and serum TC) in evaluating hepatic steatosis grade, and they were nearly 1.0000, 1.0000 and 1.000, respectively.

Conclusions

Combined application of several diagnostic methods is superior to simple diagnostic method, and could provide comprehensive, rapid, accurate evaluation of hepatic steatosis grade.     

Wilson’s disease: 31P and 1H MR spectroscopy and clinical correlation

Introduction

Proton (¹H) magnetic resonance spectroscopy (MRS) changes are noted in Wilson’s disease (WD). However, there are no studies regarding membrane phospholipid abnormality using ³¹P MRS in these patients. We aimed to analyze the striatal spectroscopic abnormalities using ³¹P and ¹H MRS in WD.

Methods

Forty patients of WD (treated, 29; untreated,11) and 30 controls underwent routine MR image sequences and in vivo 2-D ³¹P and ¹H MRS of basal ganglia using an image-selected technique on a 1.5-T MRI scanner. Statistical analysis was done using Student’s t test.

Results

The mean durations of illness and treatment were 6.2?±?7.4 and 4.8?±?5.9 years, respectively. MRI images were abnormal in all the patients. ¹H MRS revealed statistically significant reduction of N-acetyl aspartate (NAA)/choline (Cho) and NAA/creatine ratios in striatum (¹H MRS) of treated patients compared to controls. The mean values of phosphomonoesters (PME) (p?<?0.0001), phosphodiesters (PDE) (p?<?0.0001), and total phosphorus (TPh) (p?<?0.0001) were elevated in patients compared to controls. Statistically significant elevated levels of ratio of PME/PDE (p?=?0.05) observed in the striatum were noted in treated patients as compared to controls in the ³¹P MRS study. The duration of illness correlated well with increased PME/PDE [p?<?0.001], PME/TPh [p?<?0.05], and PDE/TPh [p?<?0.05] and decreased NAA/Cho [p?<?0.05] ratios. There was correlation of MRI score and reduced NAA/Cho ratio with disease severity. The PME/PDE ratio (right) was elevated in the treated group [p?<?0.001] compared to untreated group.

Conclusions

There is reduced breakdown and/or increased synthesis of membrane phospholipids and increased neuronal damage in basal ganglia in patients with WD.     

Sources of hepatic glycogen synthesis during an oral glucose tolerance test: Effect of transaldolase exchange on flux estimates

Sources of hepatic glycogen synthesis during an oral glucose tolerance test were evaluated in six healthy subjects by enrichment of a 75‐g glucose load with 6.67% [U‐¹³C]glucose and 3.33% [U‐²H₇]glucose and analysis of plasma glucose and hepatic uridine diphosphate–glucose enrichments (sampled as urinary menthol glucuronide) by ²H and ¹³C nuclear magnetic resonance. The direct pathway contribution, as estimated from the dilution of [U‐¹³C]glucose between plasma glucose and glucuronide, was unexpectedly low (36 ± 5%). With [U‐²H₇]glucose, direct pathway estimates based on the dilution of position 3 ²H‐enrichment between plasma glucose and glucuronide were significantly higher (51 ± 6%, P = 0.05). These differences reflect the exchange of the carbon 4, 5, and 6 moiety of fructose‐6‐phosphate and glyceraldehyde‐3‐phosphate catalyzed by transaldolase. As further evidence of this exchange, ²H‐enrichments in glucuronide positions 4 and 5 were inferior to those of position 3. From the difference in glucuronide positions 5 and 3 enrichments, the fraction of direct pathway carbons that experienced transaldolase exchange was estimated at 21 ± 4%. In conclusion, the direct pathway contributes only half of hepatic glycogen synthesis during an oral glucose tolerance test. Glucose tracers labeled in positions 4, 5, or 6 will give significant underestimates of direct pathway activity because of transaldolase exchange. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Comparison of R2* correction methods for accurate fat quantification in fatty liver

Purpose:

To compare the performance of fat fraction quantification using single‐R₂* and dual‐R₂* correction methods in patients with fatty liver, using MR spectroscopy (MRS) as the reference standard.

Materials and Methods:

From a group of 97 patients, 32 patients with hepatic fat fraction greater than 5%, as measured by MRS, were identified. In these patients, chemical shift encoded fat‐water imaging was performed, covering the entire liver in a single breathhold. Fat fraction was measured from the imaging data by postprocessing using 6 different models: single‐ and dual‐R₂* correction, each performed with complex fitting, magnitude fitting, and mixed magnitude/complex fitting to compare the effects of phase error correction. Fat fraction measurements were compared with co‐registered spectroscopy measurements using linear regression.

Results:

Linear regression demonstrated higher agreement with MRS using single‐R₂* correction compared with dual‐R₂* correction. Among single‐R₂* models, all 3 fittings methods performed similarly well (slope = 1.0 ± 0.06, r² = 0.89–0.91).

Conclusion:

Single‐R₂* modeling is more accurate than dual‐R₂* modeling for hepatic fat quantification in patients, even in those with high hepatic fat concentrations. J. Magn. Reson. Imaging 2013;37:414–422. © 2012 Wiley Periodicals, Inc.     

Non-invasive assessment of hepatic fat accumulation in chronic hepatitis C by H magnetic resonance spectroscopy

Background

Liver biopsy is the standard method for diagnosis of hepatic steatosis, but is invasive and carries some risk of morbidity.

Aims and methods

Quantification of hepatocellular lipid content (HCL) with non-invasive single voxel ¹H magnetic resonance spectroscopy (MRS) at 3 T was compared with histological grading and biochemical analysis of liver biopsies in 29 patients with chronic hepatitis C. Body mass index, indices of insulin resistance (homeostasis model assessment index, HOMA-IR), serum lipids and serum liver transaminases were also quantified.

Results

HCL as assessed by ¹H MRS linearly correlated (r = 0.70, p < 0.001) with histological evaluation of liver biopsies and was in agreement with histological steatosis staging in 65% of the patients. Biochemically assessed hepatic triglyceride contents correlated with HCL measured with ¹H MRS (r = 0.63, p < 0.03) and allowed discriminating between none or mild steatosis versus moderate or severe steatosis. Patients infected with hepatitis C virus genotype 3 had a higher prevalence of steatosis (62%) which was not explained by differences in body mass or whole body insulin resistance. When these patients were excluded from correlation analysis, hepatic fat accumulation positively correlated with insulin resistance in the remaining hepatitis C patients (HCL vs. HOMA-IR, r = 0.559, p < 0.020, n = 17).

Conclusion

Localized ¹H MRS is a valid and useful method for quantification of HCL content in patients with chronic hepatitis C and can be easily applied to non-invasively monitoring of steatosis during repeated follow-up measurements in a clinical setting.     

Quantitative spectroscopic imaging with in situ measurements of tissue water T1, T2, and density

The use of tissue water as a concentration standard in proton magnetic resonance spectroscopy (¹H‐MRS) of the brain requires that the water proton signal be adjusted for relaxation and partial volume effects. While single voxel ¹H‐MRS studies have often included measurements of water proton T₁, T₂, and density based on additional ¹H‐MRS acquisitions (e.g., at multiple echo or repetition times), this approach is not practical for ¹H‐MRS imaging (¹H‐MRSI). In this report we demonstrate a method for using in situ measurements of water T₁, T₂, and density to calculate metabolite concentrations from ¹H‐MRSI data. The relaxation and density data are coregistered with the ¹H‐MRSI data and provide detailed information on the water signal appropriate to the individual subject and tissue region. We present data from both healthy subjects and a subject with brain lesions, underscoring the importance of water parameter measurements on a subject‐by‐subject and voxel‐by‐voxel basis. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Noninvaive observation of hepatic glycogen formation in man by13C MRS after Orl and intravenous glucose administration

The formation of glycogen in the liver of normal volunteers was followed noninvasively with ¹³C manetic resonance spectroscopy (MRS) under tow different conditions; a) intravenous infusion of [₁-¹³C] glucose under hyperglycemic and hyperinsullinemic clamp conditions, and b) oral Intake of glucose in the form of a bolus. For the intravenous infusion, [₁-¹³C]glucose with an enrichment level of 99% was employed. The C₁ signals of α- and β-glucose could be detected in the human liver already after an infusion period of 8 min. However, an increase in the glycogen signal was observed only after a prolonged infusion of about 60 min. Changes in the glycogen signal correlated well with the time course of insulin and glucagon during the measurement. Experiments showed also that liver glycogen formation in man can be followed noninvasively by¹³C-MRS using nonlabeled glucose or [₁-¹³C]glucose with a low level of enrichment (6.6%). The use of nonlabeled glucose may therefore simplify the quantitation of net liver glycogen synthesis since it can be based directly on changes in the natural abundance ¹³C MRS glycogen signal, avoiding label dilution through the various metabolic pathways of glucose. The glucose uptake, estimated from the increase in the glycogen signal, was consistent with findings from more complex and invasive studies of glucose uptake in the liver. The average liver glycogen concentration in 12 h overnight fasted volunteers (n = 18) without any special dietary preparation was assessed to be 229 ± 34 mM (minimum = 160 mM; maximum = 274 mM).     

Avid thallium-201 uptake in hepatic carcinoid metastases

While radiolabelled somatostatin analogues sensitively detect extrahepatic carcinoid tumour, intrahepatic metastases are frequently not visualised due to somatostatin accumulation in normal hepatic tissues. We report a case of avid thallium-201 uptake in multiple hepatic carcinoid metastases using single-photon emission tomography (SPET) and compare this to a SPET technetium-99m sulphur colloid scan in the same patient. The ^99mTc sulphur colloid images demonstrate multiple focal defects at the site of known metastases in the hepatic right lobe (confirmed on both CT and surgery). However, there is avid uptake of thallium in the metastases on comparative SPET slices. ²⁰¹Tl may be a useful agent for the detection and localisation of carcinoid tumour and in particular of intrahepatic carcinoid metastases. Correspondence to: R.J. Quinn     

Preparation and biodistribution of yttrium-90 Lipiodol in rats following hepatic arterial injection

In this study, we labelled Lipiodol with yttrium-90 and analysed the biodistribution in rats after intrahepatic arterial injection. An RP-18 column (E. Merck) was used to separate⁹⁰Y from strontium-90.⁹⁰Y was retained on the column, which had been pretreated with yttrium-selective extraction reagent, di(2-ethylhexyl) phosphate, while⁹⁰Sr was washed out. A hexadentate nitrogen-donor chelating ligandN,N,N,N-tetrakis(2-ben-zymidazolylmethyl)-1,2-ethanediamine (EDTB) was synthesized by condensation of 1,2-benzenediamine and ethylene diamine tetra-acetic acid (EDTA). Lipiodol was covalently conjugated with EDTB. The final product was obtained by eluting the retained⁹⁰Y from the RP-18 column with EDTB-Lipiodol. Sixteen male rats (Sprague-Dawley) were sacrificed at 1 h, 24 h, 48 h and 72 h (four rats at each time) after injection of approximately 0.1 mCi⁹⁰Y Lipiodol via the hepatic artery. Samples of liver, spleen, muscle, lung, kidney, bone, whole blood and testis were obtained and counted to calculate the tissue concentrations. In addition, labelling efficiency and in vitro stability were determined by ITLC methods. We found that at 1 h after intrahepatic injection, most of the radiotracer was retained in the liver, but it was eliminated gradually over a few days. The radioactivity level in the lung was fair at 1 h and remained at roughly the same level throughout the study. Radioactivity in the kidney and spleen reached a relatively high level at 24 h, but declined rapidly. Bone uptake was low initially but showed an increase between 24 h and 72 h. Low concentrations of radioactivity were noted in the muscle, testis and whole blood. In the study of in vitro stability, radiochemical purity and labelling efficiency were higher than 90%, indicative of good stability. These initial results indicate that Lipiodol may be a possible carrier agent for⁹⁰Y The retention of⁹⁰Y-Lipiodol in the normal liver is high initially; however, elimination occurs over a period of a few days. Future studies should assess the biodistribution of⁹⁰Y Lipiodol in an animal model with liver cancer.