Levothyroxine effects on depressive symptoms and limbic glucose metabolism in bipolar disorder: a randomized, placebo-controlled positron emission tomography study.

Adding supraphysiologic doses of levothyroxine (L-T4) to standard treatment for bipolar depression shows promise, but the mechanisms underlying clinical improvement are unknown. In a previous pilot study, L-T4 treatment reduced depression scores and activity within the anterior limbic network. Here we extended this work in a randomized, double-blind, placebo-controlled study of patients with bipolar depression. Cerebral glucose metabolism was assessed with positron emission tomography and [F-18]fluorodeoxyglucose before and after 6 weeks of treatment with L-T4 (n=15) or placebo (n=10) in 12 volumes of interest (VOIs): the bilateral thalamus, amygdala, hippocampus, dorsal striatum and ventral striatum, and midline cerebellar vermis and subgenual cingulate cortex. Radioactivity in the VOIs, normalized to whole-brain radioactivity was taken as a surrogate index of glucose metabolism, and markers of thyroid function were assayed. Changes in brain activity and their association with clinical response were assessed using statistical parametric mapping. Adjunctive L-T4 treatment produced a significant decline in depression scores during the 6-week treatment. In patients treated with L-T4, we found a significant decrease in regional activity at P<0.05 after Bonferroni correction in the left thalamus, right amygdala, right hippocampus, left ventral striatum and the right dorsal striatum. Decreases in the left thalamus, left dorsal striatum and the subgenual cingulate were correlated with a reduction in depression scores (P<0.05 after Bonferroni correction). Placebo treatment was associated with a significant decrease in activity only in the right amygdala, and no region had a change in activity that was correlated with change in depression scores. The groups differed significantly in the relationship between the changes in depression scores and in activity in the thalamus bilaterally and the left ventral striatum. The findings provide evidence that administration of supraphysiologic thyroid hormone improves depressive symptoms in patients with bipolar disorder by modulating function in components of the anterior limbic network.

Midbrain serotonin transporters in de novo and L-DOPA-treated patients with early Parkinson's disease--a [123 I]-ADAM SPECT study.

BACKGROUND: Dopaminergic availability is known to linearly decline in Parkinson's disease (PD). In contrast, temporal characteristics of serotonergic markers like the serotonin transporter (SERT) in relation to clinical staging of PD and dopaminergic cell loss are less clear. This study investigated SERT availability using [(123) I]-ADAM and single-photon emission tomography (SPECT) in drug-naive, de novo patients, i.e., in a PD stage where dopaminergic decline starts to lead to the occurrence of the characteristic motor symptoms. METHODS: Nine de novo patients with PD and 9 age-matched healthy controls were studied. Measurements were repeated after 3 months of levodopa treatment in patients with PD, and dopaminergic transporter (DAT) binding was examined at baseline using [(123) I]-FP-CIT SPECT. RESULTS: No alterations of SERT availability were found between groups, and neither correlation between SERT and DAT nor effects of levodopa treatment on SERT was found in patients with PD. CONCLUSIONS: These preliminary findings indicate that midbrain SERT is preserved in unmedicated patients at this early stage of PD, supporting the view that serotonergic decline temporally follows dopaminergic cell loss.

Physical aspects of scintigraphy-based dosimetry for nuclear medicine therapy.

In nuclear medicine therapy the treatment of tumours by radiation exposure from internally deposited labelled antibodies or labelled peptides is currently an active field of investigation. To permit the efficient delivery of high amounts of radiation dose to tumours while limiting the radiation dose to critical organs dosimetry calculations have to be performed. These are relying on scintigraphic data being input to the well known MIRD formalism. This paper focuses on the methods and the difficulties associated with the scintigraphic determination of organ kinetics. The physical properties of the well-known scintigraphic imaging modalities, PET, SPECT and planar scintigraphy, are discussed thereby taking into account the properties of the appropriate radionuclides currently being available for therapy and dosimetry. Several arguments are given and disputed for the limited clinical use of PET and SPECT in dosimetry and the ongoing preference of planar whole-body imaging as the method of choice. The quantitative restrictions still inherent to this method are also discussed in detail. Procedural recommendations are proposed covering all processes related to data acquisition, data correction and data analysis which finally lead to reliable estimations of organ dose.

Expression of the mouse Na-K-2Cl cotransporter, mBSC2, in the terminal inner medullary collecting duct, the glomerular and extraglomerular mesangium, and the glomerular afferent arteriole.

Na-K-Cl cotransport plays an important role in the kidney in NaCl reabsorption in the thick ascending limb of Henle and a less well defined role in the inner medullary collecting duct (IMCD). Two Na-K-Cl cotransporters encoded by different genes have been identified in the mammalian kidney: BSC1/NKCC2 which localizes to the apical thick ascending limb of Henle and BSC2/NKCC1 which was isolated from a mouse IMCD cell line (mIMCD-3) but its localization has not been determined. In this study we generated a polyclonal antibody (anti-mBSC2) against the mouse BSC2/NKCC1 protein in order to characterize and localize this protein in mouse kidney. Western blot analysis with affinity-purified anti-mBSC2 showed a protein doublet of 140 and 150 kD which was most abundant in the renal papilla but also seen in cortex and outer medulla. The 140-150-kD bands were not seen with preimmune serum or with anti-mBSC2 preabsorbed with specific antigen. Immunolocalization confirmed expression of mBSC2 protein on the basolateral surface of terminal IMCD segments and demonstrated expression in the papillary surface epithelium. Immunofluorescence also revealed the unexpected presence of the BSC2 protein at the juxtaglomerular afferent arteriole, in a juxtaglomerular structure probably representing the extraglomerular mesangium, and throughout the glomerular mesangium.

Thermovoltaic properties of hornet silk.

In silk from the larval silk caps of the Oriental hornet Vespa orientalis (Hymenoptera, Vespinae), temperature-dependent changes in the electric voltage have been recorded, with rise in the voltage occurring mainly upon rise in the temperature between 10-36 degrees C. The peak voltage was measured between 32-38 degrees C and attained 240-360 mV, but with further increase in temperature, the voltage decreased, dropping to 0 mV at about 45-50 degrees C. Upon second measurement (of same silk specimen), the voltage peak usually occurred later (by 8-9 degrees C) and at higher temperature than in the first measurement. Continuous measurements during warming up to 30 degrees C followed by cooling down to 15 degrees C yielded an hysteresis between the warming "line" and the cooling "line", the former often straight and the latter usually curved. Maintaining the silk specimen at a fixed temperature for a prolonged period (hours) initially causes the voltage to rise, then remain steady, and finally drop. Boiling the silk caps in tap water for 7-10 min exerts some changes in the silk properties, mainly a decrease in voltage level. The general behavior of the silk suggests that it is a polymer endowed with the qualities of an organic semiconductor. The various properties of the larval silk are discussed in great detail.

Corrections of arterial input function for dynamic H215O PET to assess perfusion of pelvic tumours: arterial blood sampling versus image extraction.

Assessment of perfusion with 15O-labelled water (H215O) requires measurement of the arterial input function (AIF). The arterial time activity curve (TAC) measured using the peripheral sampling scheme requires corrections for delay and dispersion. In this study, parametrizations with and without arterial spillover correction for fitting of the tissue curve are evaluated. Additionally, a completely noninvasive method for generation of the AIF from a dynamic positron emission tomography (PET) acquisition is applied to assess perfusion of pelvic tumours. This method uses a volume of interest (VOI) to extract the TAC from the femoral artery. The VOI TAC is corrected for spillover using a separate tissue TAC and for recovery by determining the recovery coefficient on a coregistered CT data set. The techniques were applied in five patients with pelvic tumours who underwent a total of 11 examinations. Delay and dispersion correction of the blood TAC without arterial spillover correction yielded in seven examinations solutions inconsistent with physiology. Correction of arterial spillover increased the fitting accuracy and yielded consistent results in all patients. Generation of an AIF from PET image data was investigated as an alternative to arterial blood sampling and was shown to have an intrinsic potential to determine the AIF noninvasively and reproducibly. The AIF extracted from a VOI in a dynamic PET scan was similar in shape to the blood AIF but yielded significantly higher tissue perfusion values (mean of 104.0 +/- 52.0%) and lower partition coefficients (-31.6 +/- 24.2%). The perfusion values and partition coefficients determined with the VOI technique have to be corrected in order to compare the results with those of studies using a blood AIF.

[Determination of ventricular volumes in coronary artery disease: comparison of two gated SPECT analysis tools with MRI]. / Bestimmung ventrikulärer Volumina bei koronarer Herzerkrankung: Vergleich zweier Gated-SPECT-Analyseverfahren mit MRT.

AIM: Comparison of two gated SPECT analysis tools -- gated SPECT quantification (GSQ) and emory cardiac toolbox (ECT) -- in patients with coronary artery disease (CAD) and severely impaired left ventricular function (preoperative: EF <35% by cardiac catheter). PATIENTS, METHODS: A total of 56 gated SPECT examinations (one-day hybrid-protocol with (201)Tl-chloride for rest and (99m)Tc-sestamibi for stress applied during low-dose dobutamine stress MR-examination; temporal resolution; 8 phases per cardiac cycle) were performed in 36 patients (31 preoperatively, 25 postoperatively) and compared with MRI in 48 cases. Left ventricular end-diastolic (LV-EDV) and end-systolic (LV-ESV) volumes as well as the left ventricular ejection fraction (LV-EF) were calculated. RESULTS: The total volumetric assessment by both analysis algorithms (n = 56) showed good intraclass correlation coefficients preoperatively (n = 31), but even better postoperatively (n = 25). The mean reconstruction time was approximately 3 minutes ( +/- 2 SD) for GSQ and 15 minutes ( +/- 5 SD) for ECT. In comparison to MRI the results of both analysis tools also correlated well, but the agreement decreased in the presence of scared tissue. The mean LV-EF (MRI) preoperatively was 30.4%, in 6/36 patients above the values calculated from cardiac catheter, postoperatively 34.6%. CONCLUSION: Both gated SPECT analysis tools showed reliable volumetric assessments in high-risk patients with CAD and severely reduced LV-EF in comparison to MRI, with advantages for GSQ in terms of postprocessing time. However, for the calculation of LV-EF a markedly lower concordance with MR-results was observed for both methods depending on the presence of myocardial scars.

Evaluation of patients with liver metastases from colorectal cancer for locally ablative treatment with laser induced thermotherapy. Impact of PET with 18F-fluorodeoxyglucose on therapeutic decisions.

PURPOSE: Before locally ablative treatment of colorectal liver metastases, patients have to be carefully evaluated to decide whether this is the adequate therapy. In this study we determined the value of FDG-PET in comparison to conventional staging procedures. PATIENTS, METHODS: In 68 consecutive patients referred for laser induced thermotherapy (LITT) of liver metastases from colorectal cancer, pretherapeutic staging with conventional imaging (thoracic and abdominal CT, liver MRI, chest X-ray) and FDG-PET was performed. The examinations were analysed separately and blinded. Based on the staging information, therapeutic decisions were made by an interdisciplinary review board according to a standardized algorithm. The results were compared between conventional imaging and FDG-PET, and were validated by clinical follow up data and histopathology, respectively. RESULTS: On FDG-PET 210 lesions were interpreted as tumour manifestations. 48 of these were not seen on conventional imaging (true positive, n = 46). In contrast, 24 lesions were visualized by conventional imaging only (true positive, n = 12). Compared to conventional imaging, discrepant findings on FDG-PET led to treatment modifications in 25 patients (37%); these were correct in 20/25 patients. According to the actual treatment course, the inadequate treatment modifications in the remaining 5 patients were avoided by further diagnostic procedures (i.e. biopsies). CONCLUSION: In the evaluation of patients with known liver metastases from colorectal cancer before LITT, FDG-PET depicts relevant findings subsidiary to conventional imaging and thus is of high value for therapeutic decision making.

A family with pheochromocytoma-paraganglioma inherited tumour syndrome. Serial 18F-DOPA PET/CT investigations.

AIM: Hereditary pheochromocytoma-paraganglioma syndromes are characterized by multiple pheochromocytomas (PCC) and paragangliomas (PGLs), inherited in an autosomal dominant manner. Early detection and removal of tumours may prevent or minimize complications related to mass effects and malignant transformation. Having confirmed the diagnosis, it is important to localize the tumours and reveal their extent preoperatively. This study aimed to introduce 18F-DOPA PET/CT as a highly sensitive non-invasive diagnostic tool for early detection of mass lesions in patients with pheochromocytoma-paraganglioma inherited tumour syndrome and to report about its impact on patient management. PATIENTS, METHODS: We are currently supervising one of the largest documented families in Germany with genetically determined SDHD gene mutation. We performed 18F-DOPA PET/CT in order to detect tumours in asymptomatic gene carriers and enable subsequent surgical therapy. RESULTS: In seven patients undergoing 12 18F-DOPA PET/CT scans 17 lesions have been detected. Three of these lesions, located in the head and neck region, have had no morphologic correlate in CT and one had also no morphologic correlate in MRI. Of the six histologically analyzed lesions five have been tumors (PGL or PCC) and one has been a nodular hyperplasia. This means the 18F-DOPA PET/CT scan in our study group had a sensitivity of 83%. 18F-DOPA PET/CT investigations lead to change in the management in 5/7 studied patients (70%). CONCLUSION: The benefits of PET/CT in detection of pheochromocytoma and paraganglioma are well documented, but we are the first to use this technique for screening of a rare hereditary disease (estimated prevalence 0.3/100 000).

Bedside microdialysis reflects dysfunction of cerebral energy metabolism in patients with aneurysmal subarachnoid hemorrhage as confirmed by 15 O-H2 O-PET and 18 F-FDG-PET.

OBJECTIVE: To compare microdialysis (MD) and positron emission tomography (PET) in the detection of ischemia in aneurysmal subarachnoid hemorrhage (SAH) patients. METHODS: 15 SAH patients (13F/2M, 48+/-13 years, WFNS Grade I-V) were prospectively included in the study. A MD-catheter was inserted into the brain parenchyma most likely to be affected by vasospasm directly after aneurysm clipping. Glucose, pyruvate, lactate, glutamate and glycerol were analyzed hourly (CMA 600). 15O-H2O-PET scans (n=10) and 18F-FDG-PET scans (n=13) were performed between the day 2 and 17 after SAH. 15O-H2O-PET data were merged with CT scans to provide quantification of rCBF within the MD-ROI (rCBFMD; Amira, ZIB Berlin, Germany). 18F-FDG-PET data were evaluated visually by visual analysis. RESULTS: Regions of glucose hypometabolism were observed in 10 patients with symptoms of ischemia. Their rCBF was lower compared to asymptomatic patients (p<0.05). The MD levels of glutamate, lactate, the L/P ratio and glycerol were significantly higher in symptomatic than asymptomatic patients (p<0.05). Out of all measured MD parameters, glutamate showed the closest correlation with rCBF (r=-0.66, p=0.014). Microdialysis parameters were well correlated with glucose hypometabolism (18F-FDG-PET) and symptoms of ischemia. However, the threshold for a metabolic derangement was above the limits of cerebral ischemia defined by PET. CONCLUSION: MD is a useful tool to monitor ischemia, especially in patients with high-grade SAH.

Impact of FDG PET on patients with differentiated thyroid cancer who present with elevated thyroglobulin and negative 131I scan.

UNLABELLED: FDG PET is increasingly performed in patients with differentiated thyroid cancer who present with elevated human thyroglobulin (hTG) levels and negative 131I scan. The aim of this study was to evaluate the impact of FDG PET on treatment in these patients. METHODS: A total of 118 FDG PET studies were performed on 64 patients, and follow-up data were available for all patients. Whole-body images were acquired 1 h after intravenous injection of 370 MBq (10 mCi) FDG using a PET scanner with an axial field of view of 16.2 cm. Tumor-suspicious FDG PET studies were evaluated by histology, cytology, 131I uptake, CT or MRI, and follow-up of hTg levels. The therapeutic consequence was noted for each patient. Moreover, results of FDG PET were correlated with hTg levels. RESULTS: Forty-four patients had positive scans, which were proven to be true-positive in 34 patients, whereas 7 patients had false-positive findings. Two patients exhibited a secondary malignancy. One patient did not fit in any category, having true-positive, false-positive, and false-negative findings. On the other hand, 20 patients had negative scans. These were true-negative findings in 5 patients, whereas the remaining 15 patients had false-negative results. Accordingly, the positive predictive value of FDG PET was 83% (34/41), whereas the negative predictive value was 25% (5/20). Treatment was directly changed in 19 of 34 patients with true-positive PET studies: 18 patients had further surgery, and 4 patients were referred for external irradiation, 3 of them after incomplete removal of local recurrences. FDG PET showed widespread disease in 7 patients; thus, palliative treatment, rather than curative therapy, was initiated. True-positive FDG PET findings were correlated positively with increasing hTg levels (i.e., FDG PET was true-positive in 11%, 50%, and 93% of patients with hTg levels of <10, 10-20, and >100 microg/L, respectively). CONCLUSION: FDG PET is a valuable diagnostic tool in patients with differentiated thyroid cancer who present with increased hTg levels and negative 131I scans because it permits selection of patients for surgery, which may be curative. FDG PET is most promising at hTg levels of >10 microg/L.

Nonconventional carbon additions to azomethines. aryl amination/indoline synthesis by direct aryl radical addition to azomethine nitrogen.

[reaction: see text]. The generality of a new method for aryl amination has been defined. Ketimines derived from o-bromophenethylamine cyclize to the N-substituted indoline when treated with nBu3SnH and a radical initiator. The pH-neutral conditions tolerate base- and acid-sensitive functionality. The observed regioselectivity is nonconventional for addition reactions involving carbon radicals and carbon-heteroatom pi-bonds.

A highly enantioselective conjugate reduction of 3-arylinden-1-ones using bakers' yeast for the preparation of (S)-3-arylindan-1-ones.

[formula: see text] The bakers' yeast reduction of 3-(1,3-benzodioxol-5-yl)-6-propoxy-1H-inden-1-one 4 has been shown to give (S)-3-(1,3-benzodioxol-5-yl)-2,3-dihydro-6-propoxy-1H-indan-1-one 6 in 65% yield with high enantioselectivity (> 99.0% ee), a key intermediate for the synthesis of the endothelin receptor antagonist SB 217242. In addition, the substituted 3-arylinden-1-ones 10a-e gave equally high enantioselectivity for the 3-arylindan-1-one products 13a-e. Mechanistic studies of the reaction indicate the operative pathway to be an asymmetric conjugate reduction, wherein the hydride transfer from NAD(P)H occurs from the Re-face of the indenone substrate.

Early age of onset in fatal familial insomnia. Two novel cases and review of the literature.

Fatal familial insomnia (FFI) is a prion disease exhibiting the PRNP D178N/129M genotype. Features of this autosomal dominant illness are progressive insomnia, dysautonomia, myoclonus, cognitive decline and motor signs associated with thalamic nerve cell loss and gliosis. In contrast to the new variant of Creutzfeldt-Jakob disease (vCJD) the onset of FFI is in middle to late adulthood. We report two male patients who belong to a large German FFI kindred. They were examined clinically, and postmortem neuropathological examination was carried out in collaboration with the German reference centre for prion disease. Additionally, the prion protein gene (PRNP) was analysed. To identify further patients with disease onset under 30 years of age a comprehensive literature review was carried out. Two male patients presented with typical symptoms of FFI at the age of 23 and 24 years. In their kindred, the age of onset has never before been under 44 years of age. Our literature review identified five additional early onset cases who died at age 21 to 25 years. In all 22 reviewed FFI families the median manifestation age was 49.5 years. Although phenotypic variability of FFI is common, age of onset under 30 years has been considered to be a hallmark of vCJD with a mean manifestation at 27 years of age. Our findings underline that in addition to vCJD, FFI must be considered in cases of young-onset prion disease. This has considerable impact on clinical management and genetic counselling.

Comparison of different cardiac MRI sequences at 1.5 T/3.0 T with respect to signal-to-noise and contrast-to-noise ratios - initial experience.

PURPOSE: To compare image quality, signal-to-noise (SNR) and contrast-to-noise ratios (CNR) of different MRI sequences for cardiac imaging at 1.5 T and 3.0 T in volunteers. MATERIAL AND METHODS: 10 volunteers (5 male, 5 female) with a mean age of 33 years (+/- 8) without any history of cardiac diseases were examined on a GE Signa 3.0 T and a GE Signa 1.5 T TwinSpeed Excite (GE Medical Systems, Milwaukee, WI, USA) scanner using a 4-element phased array surface coil (same design) on the same day. For tissue characterization ECG gated Fast Spinecho (FSE) T (1)- (Double IR), T (1)-STIR (Triple IR) and T (2)-weighted sequences in transverse orientation were used. For functional analysis a steady state free precession (SSFP - FIESTA) sequence was performed in the 4-chamber, 2-chamber long axis and short axis view. The flip angle used for the SSFP sequence at 3.0 T was reduced from 45 degrees to 30 degrees to keep short TR times while staying within the pre-defined SAR limitations. All other sequence parameters were kept constant. RESULTS: All acquisitions could successfully be completed for the 10 volunteers. The mean SNR 3.0 T compared to 1.5 T was remarkably increased (p < 0.05) for the T (2) - (160 % SNR increase), the STIR-T (1)- (123 %) and the T (1)- (91 %) weighted FSE. Similar results were found comparing CNR at 3.0 T and 1.5 T. The mean SNR achieved using the SSFP sequences was more than doubled by 3.0 T (150 %), but did not have any significant effect on the CNR. The image quality at 3.0 T did not appear to be improved, and was considered to be significantly worse when using SSFP sequences. Artefacts like shading in the area of the right ventricle (RV) were found to be more present at 3.0 T using FSE sequences. After a localized shim had been performed in 5/10 volunteers at the infero-lateral wall of the left ventricle (LV) with the SSFP sequences at 3.0 T no significant increase in artefacts could be detected. CONCLUSIONS: In all cardiac FSE sequences, SNR and CNR at 3.0 T were found to be increased compared to 1.5 T without any major changes of the sequence parameters. The adjusted SSFP sequences fulfilled the expected increase in SNR at 3.0 T but showed no increase in CNR. On the contrary, the overall image quality did not change or was even found to be significantly lower for the SSFP and the FSE sequences at the free wall of the RV. Nevertheless, the results are encouraging for the use of 3.0 T for cardiac tissue characterization and new applications with progressing use of parallel imaging.

Use of statistical parametric mapping of (18) F-FDG-PET in frontal lobe epilepsy.

AIM: Evaluation of the use of statistical parametrical mapping (SPM) of FDG-PET for seizure lateralization in frontal lobe epilepsy. PATIENTS: 38 patients with suspected frontal lobe epilepsy supported by clinical findings and video-EEG monitoring. METHOD: Statistical parametrical maps were generated by subtraction of individual scans from a control group, formed by 16 patients with negative neurological/psychiatric history and no abnormalities in the MR scan. The scans were also analyzed visually as well as semiquantitatively by manually drawn ROIs. RESULTS: SPM showed a better accordance to the results of surface EEG monitoring compared with visual scan analysis and ROI quantification. In comparison with intracranial EEG recordings, the best performance was achieved by combining the ROI based quantification with SPM analysis. CONCLUSION: These findings suggest that SPM analysis of FDG-PET data could be a useful as complementary tool in the evaluation of seizure focus lateralization in patients with supposed frontal lobe epilepsy.

Medicinal uses of South American palms.

Palms are the most versatile group of plants used by man, providing all of the basic necessities (food, shelter, fuel and fiber) as well as many ameliorants (spices, oils, waxes, gums, poisons and medicines). The importance of palms in the pharmacopoeias of South American Indians has received little attention. This paper presents the results of a literature search on the medicinal uses of South American palms and suggests that phytochemical screening of these species might result in the identification of new and useful biodynamic compounds.

Mark Plotkin, PhD: in search of plants that heal. Interview by Bonnie Horrigan.

Ethnobotantist Mark Plotkin, PhD, spent much of the last decade in the rain forests of South America, learning about curative plants and medical practices from the tribal shamans. Through his work with indigenous people in Brazil, French Guiana, Suriname, and Venezuela, he has categorized more than 300 shaman plant cures. Plotkin studied ethnobotany at Harvard, Yale, and Tufts, and is the first botanist to receive the San Diego Zoological Society's Conservation Medal. He previously served as director of plant conservation at the World Wildlife Fund, the world's largest conservation organization, and as vice president of Conservation International. Founder of the "Shaman's Apprentice Program," which encourages younger tribal members to apprentice under the aging shamans, Plotkin currently devotes his time to curative plant research, consultation, lecturing, writing, and fund raising for his new organization, the Conservation and Ethnobiology Alliance. He has published numerous scientific articles and is the author of the popular book, Tales of a Shaman's Apprentice.

Virola: a promising genus for ethnopharmacological investigation.

Data are now available on the antifungal use of Virola from four countries and some 14 different tribes of Indians in these countries who employ the Virola exudate for the same or similar purposes. Three of the five methods of ethnobotanical investigation proposed by Schultes and Swain in 1976 have been employed in this ethnobotanical research. Furthermore, both of the present authors have successfully employed this antifungal treatment themselves. Given that deep fungal infections of the skin are often considered incurable with medications currently in use, further laboratory analysis of Virola resin should be undertaken as soon as possible.

Multi-centre calibration of an adaptive thresholding method for PET-based delineation of tumour volumes in radiotherapy planning of lung cancer.

PURPOSE: To evaluate the calibration of an adaptive thresholding algorithm (contrast-oriented algorithm) for FDG PET-based delineation of tumour volumes in eleven centres with respect to scanner types and image data processing by phantom measurements. METHODS: A cylindrical phantom with spheres of different diameters was filled with FDG realizing different signal-to-background ratios and scanned using 5 Siemens Biograph PET/CT scanners, 5 Philips Gemini PET/CT scanners, and one Siemens ECAT-ART PET scanner. All scans were analysed by the contrast-oriented algorithm implemented in two different software packages. For each site, the threshold SUVs of all spheres best matching the known sphere volumes were determined. Calibration parameters a and b were calculated for each combination of scanner and image-analysis software package. In addition, "scanner-type-specific" calibration curves were determined from all values obtained for each combination of scanner type and software package. Both kinds of calibration curves were used for volume delineation of the spheres. RESULTS: Only minor differences in calibration parameters were observed for scanners of the same type (Δa ≤4%, Δb ≤14%) provided that identical imaging protocols were used whereas significant differences were found comparing calibration parameters of the ART scanner with those of scanners of different type (Δa ≤60%, Δb ≤54%). After calibration, for all scanners investigated the calculated SUV thresholds for auto-contouring did not differ significantly (all p>0.58). The resulting sphere volumes deviated by less than -7% to +8% from the true values. CONCLUSION: After multi-centre calibration the use of the contrast-oriented algorithm for FDG PET-based delineation of tumour volumes in the different centres using different scanner types and specific imaging protocols is feasible.