Increase in brown adipose tissue activity after weight loss in morbidly obese subjects.

CONTEXT: Stimulation of thermogenesis in brown adipose tissue (BAT) is a potential target to treat obesity. We earlier demonstrated that BAT activity is relatively low in obese subjects. It is unknown whether BAT can be recruited in adult humans. OBJECTIVE: To study the dynamics of BAT, we observed BAT activity in morbidly obese subjects before and after weight loss induced by bariatric surgery. DESIGN: This was an observational prospective cohort study. SETTING: The study was conducted at a referral center. PATIENTS: Ten morbidly obese subjects eligible for laparoscopic adjustable gastric banding surgery were studied before and 1 yr after bariatric surgery. MAIN OUTCOME MEASURE: The main outcome measure was BAT activity, as determined after acute cold stimulation using (18)F-fluorodeoxyglucose positron emission tomography and computed tomography. RESULTS: Before surgery, only two of 10 subjects showed active BAT. One year after surgery, the number of subjects with active BAT was increased to five. After weight loss, BAT-positive subjects had significantly higher nonshivering thermogenesis compared with BAT-negative subjects (P < 0.05). CONCLUSIONS: The results show that in humans BAT can be recruited in the regions in which it was also reported in lean subjects before. These results for the first time show recruitment of BAT in humans and may open the door for BAT-targeted treatments of obesity.

Long-term prognosis of patients with cardiac syndrome X: a review.

AIMS: Follow-up studies of patients with cardiac syndrome X (CSX) generally report good prognosis. However, some recent studies report an adverse outcome for women. METHODS AND RESULTS: Structured literature search and meta-analysis for studies regarding prognosis of cardiac syndrome X patients. We identified 85 studies, ultimately selecting 16 for inclusion. Meta-analysis yielded a pooled major cardiac event percentage of 1.5% per 5 years and a pooled vascular event percentage of 4.8% per 5 years (n = 16 studies, n = 1694 patients). Fourteen studies reported upon the recurrence rate of angina pectoris: the pooled percentage of angina recurrence was 55% (n = 1336 patients). CONCLUSION: The present review of recent archival literature demonstrates an overall major cardiac event rate of 1.5% per 5 years. Although this is an excellent prognosis for CSX patients, the quality of life is impaired because of the high recurrence rate of angina pectoris (55%).

Hard beta and gamma emissions of 124I. Impact on occupational dose in PET/CT.

AIM: The hard beta and gamma radiation of 124I can cause high doses to PET/CT workers. In this study we tried to quantify this occupational exposure and to optimize radioprotection. METHODS: Thin MCP-Ns thermoluminescent dosimeters suitable for measuring beta and gamma radiation were used for extremity dosimetry, active personal dosimeters for whole-body dosimetry. Extremity doses were determined during dispensing of 124I and oral administration of the activity to the patient, the body dose during all phases of the PET/CT procedure. In addition, dose rates of vials and syringes as used in clinical practice were measured. The procedure for dispensing 124I was optimized using newly developed shielding. RESULTS: Skin dose rates up to 100 mSv/min were measured when in contact with the manufacturer's vial containing 370 MBq of 124I. For an unshielded 5 ml syringe the positron skin dose was about seven times the gamma dose. Before optimization of the preparation of 124I, using an already reasonably safe technique, the highest mean skin dose caused by handling 370 MBq was 1.9 mSv (max. 4.4 mSv). After optimization the skin dose was below 0.2 mSv. CONCLUSION: The highly energetic positrons emitted by 124I can cause high skin doses if radioprotection is poor. Under optimized conditions occupational doses are acceptable. Education of workers is of paramount importance.

Brown adipose tissue in morbidly obese subjects.

BACKGROUND: Cold-stimulated adaptive thermogenesis in brown adipose tissue (BAT) to increase energy expenditure is suggested as a possible therapeutic target for the treatment of obesity. We have recently shown high prevalence of BAT in adult humans, which was inversely related to body mass index (BMI) and body fat percentage (BF%), suggesting that obesity is associated with lower BAT activity. Here, we examined BAT activity in morbidly obese subjects and its role in cold-induced thermogenesis (CIT) after applying a personalized cooling protocol. We hypothesize that morbidly obese subjects show reduced BAT activity upon cold exposure. METHODS AND FINDINGS: After applying a personalized cooling protocol for maximal non-shivering conditions, BAT activity was determined using positron-emission tomography and computed tomography (PET-CT). Cold-induced BAT activity was detected in three out of 15 morbidly obese subjects. Combined with results from lean to morbidly obese subjects (n = 39) from previous study, the collective data show a highly significant correlation between BAT activity and body composition (P<0.001), respectively explaining 64% and 60% of the variance in BMI (r = 0.8; P<0.001) and BF% (r = 0.75; P<0.001). Obese individuals demonstrate a blunted CIT combined with low BAT activity. Only in BAT-positive subjects (n = 26) mean energy expenditure was increased significantly upon cold exposure (51.5±6.7 J/s versus 44.0±5.1 J/s, P = 0.001), and the increase was significantly higher compared to BAT-negative subjects (+15.5±8.9% versus +3.6±8.9%, P = 0.001), indicating a role for BAT in CIT in humans. CONCLUSIONS: This study shows that in an extremely large range of body compositions, BAT activity is highly correlated with BMI and BF%. BAT-positive subjects showed higher CIT, indicating that BAT is also in humans involved in adaptive thermogenesis. Increasing BAT activity could be a therapeutic target in (morbid) obesity.

Potential of integrated [18F] fluorodeoxyglucose positron-emission tomography/CT in identifying vulnerable carotid plaques.

BACKGROUND AND PURPOSE: There is a need for improved risk stratification of patients with TIA/stroke and carotid atherosclerosis. The purpose of this study was to prospectively investigate the potential of integrated (18)F-FDG PET/MDCT in identifying vulnerable carotid plaques. MATERIALS AND METHODS: Fifty patients with TIA/stroke with an ipsilateral carotid plaque causing <70% stenosis and a plaque on the contralateral asymptomatic side underwent integrated (18)F-FDG PET/MDCT within 36.1 ± 20.0 days (range, 9-95 days) of the last symptoms. Carotid plaque (18)F-FDG uptake was measured as both the mean and maximum blood-normalized SUV, known as the TBR. Using MDCT, we assessed volumes of vessel wall and individual plaque components. RESULTS: Mean TBR was only significantly larger in the ipsilateral plaques of patients who were imaged within 38 days (1.24 ± 0.04 [SE] versus 1.17 ± 0.05, P = .014). This also accounted for maximum TBR (1.53 ± 0.06 versus 1.42 ± 0.06, P = .015). MDCT-assessed vessel wall and LRNC volumes were larger in ipsilateral plaques of all patients (982.3 ± 121.3 versus 811.3 ± 106.6 mm(3), P = .016; 164.7 ± 26.1 versus 134.3 ± 35.2 mm(3), P = .026, respectively). CONCLUSIONS: In the present study, (18)F-FDG PET only detected significant differences between ipsilateral and contralateral asymptomatic plaques in patients with TIA/stroke who were imaged within 38 days, whereas MDCT detected larger vessel wall and LRNC volumes, regardless of time after symptoms. In view of the substantial overlap in measurements of both sides, it remains to be determined whether the differences we found will be clinically meaningful.

Blocking the saphenofemoral junction during ultrasound-guided foam sclerotherapy-- assessment of a presumed safety-measure procedure.

OBJECTIVES: Ultrasound-guided foam sclerotherapy (UGFS) is a technique in which a mixture of sclerosing drug and gas is used to treat varicose veins. Several authors have demonstrated transient systemic effects after UGFS. These effects are not well understood but probably originate from a systemic distribution of the sclerosing foam. Therefore, safety measures have been developed to prevent foam from flowing into the deep venous system. The aim of the study is to evaluate whether blockage of the saphenofemoral (SF) junction by either manual compression or surgical ligation prevents microbubbles from leaking into the deep venous circulation. METHODS: To detect the distribution of microbubbles, radioactive pertechnetate (99mTcO4-) was added to the foam solution. Initially, in vitro trials were performed in the laboratory to investigate the effect of 99mTc on foam stability. The time taken for foam to liquefy was measured for foam alone and for the mixture with 99mTc. In subsequent research, eight varicose great saphenous veins (GSVs) were treated by UGFS. In three patients, this treatment was preceded by surgical ligation of the SF junction. In three patients, the groin was manually compressed during UGFS. In two patients, UGFS was performed without compression of the groin. RESULTS: In vitro, 99mTc did not influence foam stability; after 2.6 min all foam had reduced to liquid, regardless of whether 99mTc had been added or not. In vivo trials showed that all patients showed a decrease in the cumulative amount of 99mTc detected in the GSV following polidocanol-99mTc mixture injection. However, the decrease of radioactivity was slightly reduced when compression or ligation of the SF junction was performed. CONCLUSIONS: Blocking the SF junction during UGFS using either manual compression or ligation does not prevent, but may reduce the flow of foam into the femoral vein.

Definitions and incidence of cardiac syndrome X: review and analysis of clinical data.

There is no consensus regarding the definition of cardiac syndrome X (CSX). We systematically reviewed recent literature using a standardized search strategy. We included 57 articles. A total of 47 studies mentioned a male/female distribution. A meta-analysis yielded a pooled proportion of females of 0.56 (n = 1,934 patients, with 95% confidence interval: 0.54-0.59). As much as 9 inclusion criteria and 43 exclusion criteria were found in the 57 articles. Applying these criteria to a population with normal coronary angiograms and treated in 1 year at a general hospital, the attributable CSX incidence varied between 3 and 11%. The many inclusion and exclusion criteria result in a wide range of definitions of CSX and these have large effects on the incidence. This shows the need for a generally accepted definition of CSX.

Cold-activated brown adipose tissue in healthy men.

BACKGROUND: Studies in animals indicate that brown adipose tissue is important in the regulation of body weight, and it is possible that individual variation in adaptive thermogenesis can be attributed to variations in the amount or activity of brown adipose tissue. Until recently, the presence of brown adipose tissue was thought to be relevant only in small mammals and infants, with negligible physiologic relevance in adult humans. We performed a systematic examination of the presence, distribution, and activity of brown adipose tissue in lean and obese men during exposure to cold temperature. Brown-adipose-tissue activity was studied in relation to body composition and energy metabolism. METHODS: We studied 24 healthy men--10 who were lean (body-mass index [BMI] [the weight in kilograms divided by the square of the height in meters], < 25) and 14 who were overweight or obese (BMI, > or = 25)--under thermoneutral conditions (22 degrees C) and during mild cold exposure (16 degrees C). Putative brown-adipose-tissue activity was determined with the use of integrated (18)F-fluorodeoxyglucose positron-emission tomography and computed tomography. Body composition and energy expenditure were measured with the use of dual-energy x-ray absorptiometry and indirect calorimetry. RESULTS: Brown-adipose-tissue activity was observed in 23 of the 24 subjects (96%) during cold exposure but not under thermoneutral conditions. The activity was significantly lower in the overweight or obese subjects than in the lean subjects (P=0.007). BMI and percentage of body fat both had significant negative correlations with brown adipose tissue, whereas resting metabolic rate had a significant positive correlation. CONCLUSIONS: The percentage of young men with brown adipose tissue is high, but its activity is reduced in men who are overweight or obese. Brown adipose tissue may be metabolically important in men, and the fact that it is reduced yet present in most overweight or obese subjects may make it a target for the treatment of obesity.

99mTc Nanocoll: a radiopharmaceutical for sentinel node localisation in breast cancer--in vitro and in vivo results.

This study evaluated labelling efficiency and radiochemical purity of (99m)Tc colloid albumin to identify an optimal labelling protocol for sentinel node detection. Results indicate that a 72 h eluate is not recommended for high specific labelling of (99m)Tc colloid albumin. Ex vivo, significantly higher count rates were reached using a 2h eluate in vacuum or nitrogen. Labelling 26 MBq/microg (99m)Tc colloid albumin with a 2 h eluate under nitrogen is recommended because of the ease of labelling.

Association between anxiety disorder and the extent of ischemia observed in cardiac syndrome X.

BACKGROUND: A possible link between the heart and brain has been reported for cardiac syndrome X. Anxiety disorder could be a pathophysiological mechanism for this cardiac chest pain. To the authors' knowledge, a quantitative analysis correlating anxiety with the extent of ischemia has not been done. METHODS AND RESULTS: In this pilot study, we evaluated 20 patients with typical chest pain and completely normal coronary angiograms. These patients were screened with the State Scale and Trait Scale of the State-Trait Anxiety Inventory (STAI). All patients underwent myocardial perfusion scintigraphic imaging. The scintigrams were scored by three experienced readers having no knowledge of the STAI screening results. Patients with a low trait anxiety had significantly less ischemic segments on the myocardial perfusion imaging than patients with a high trait anxiety (1.8 +/- 1.9 vs 3.5 +/- 0.6, P < .05). For state anxiety, no significant differences could be found. CONCLUSION: Cardiac syndrome X patients with high trait anxiety are at risk of having more ischemia.

Identifying vulnerable carotid plaques by noninvasive imaging.

Stroke results in considerable morbidity and mortality. Prevention is therefore of particular importance. On the basis of large clinical trials, carotid endarterectomy (CEA) is performed in selected patient groups to prevent stroke. Patient symptomatology and degree of carotid stenosis are the main clinical grounds to perform CEA. However, many individual patients undergo surgery with its attendant risks without taking advantage of it, whereas in others CEA is probably incorrectly withheld. There is therefore an urgent need for new adjuncts to identify high-risk subgroups of patients who particularly benefit from potentially hazardous interventions. Multiple noninvasive imaging modalities have shown their potential to differentiate high-risk, vulnerable carotid plaques from stable plaques. The ultimate goal is to implement one or a combination of these imaging modalities in daily clinical practice. This review gives an up-to-date overview of the clinical potential of these imaging modalities in identifying patients with carotid atherosclerosis who are at high risk for developing stroke. Advantages and limitations of each imaging technique are outlined. Additionally, recommendations for future research are presented.

The role of (124)I-PET in diagnosis and treatment of thyroid carcinoma.

Iodine-124 is a positron-emitting iodine isotope, enabling measurement of iodine uptake using positron emission tomography (PET). There is a number of situations where the use of (124)I-PET/computed tomography (CT) can improve the current clinical practice in the diagnosis and treatment of thyroid cancer. Firstly, (124)I-PET/CT can aid in the staging of patients, because of better detection of metastatic disease and measurement of metabolic tumour volume, and thus separate low-risk from high risk patients. Secondly, the much higher sensitivity and spatial resolution of PET compared to gamma scintigraphy can also improve detection of recurrent disease. Furthermore, (124)I-PET can be used for patient-specific radioiodine therapy radiation dosimetry. Simultaneous administration of the therapeutic dose of (131)I and a tracer dose of (124)I allows for accurate measurement of iodine uptake during therapy. The decay scheme of (124)I, with few positrons and many gamma rays emitted per decay, often simultaneously, poses a challenge to quantitative PET imaging. Improved correction methods and the use of last-generation PET/CT scanners with faster electronics and better energy resolution can overcome this.

(99M)Technetium-sestamibi scintimammography in non-palpable breast lesions found on screening X-ray mammography.

OBJECTIVE: The sensitivity and specificity of (99m)Tc-sestamibi scintimammography in patients with non-palpable breast lesions diagnosed by screening mammography and the value of (99m)Tc-sestamibi to detect axillary lymph node metastases was determined. METHODS: Between September 2000 and December 2003, 103 females with non-palpable breast lesions were included for further evaluation. X-ray mammography was repeated and 99mTc-sestamibi scintimammography performed within one-week. Anterior, and left and right lateral images were obtained. The scintimammography was analysed by 2 experienced observers who were blinded to the clinical, pathological, and radiological results. The sensitivity and specificity of scintimammography to diagnose non-palpable lesion(s), including the axillary regions, was compared with histopathology, clinical, and radiological follow up. RESULTS: Two patients (one non-small lung cancer and one non-Hodgkin's disease) were excluded. Both showed (99m)Tc-sestamibi avid lesions in the breast and axillary region. In the remaining 101 patients, 37 true positive (TP), 4 false positive (FP), 52 true negative (TN), and 8 false negative (FN) breast carcinomas were found. The specificity was 92.8%, sensitivity 82.2%, positive predictive value (PPV) 90.2%, and negative predictive value (NPV) 86.6%. (99m)Tc-sestamibi scintimammography showed axillary lesions in 5/15 (33%) patients with axillary lymph node metastasis. CONCLUSION: In patients with non-palpable lesions diagnosed by screening- X-ray-mammography, (99m)Tc-sestamibi scintimammography provided high specificity and PPV. Furthermore, (99m)Tc-sestamibi scintimammography detected 33% of patients with axillary lymph node metastases. Therefore, (99m)Tc-sestamibi scintimammography could be of incremental value in the surgical work-up of these patients.

Proteus syndrome: a rare cause of hemihypertrophy and macrodactyly on bone scanning.

Proteus syndrome is a rare, sporadic genetic disorder characterized by overgrowth of multiple different tissues in a mosaic pattern. It is associated with connective tissue nevi, epidermal nevi, disproportionate overgrowth of multiple tissues, vascular malformations, characteristic tumors, and specific facial anomalies. Joseph Merrick, popularly known as the Elephant Man, is now believed to have suffered from Proteus syndrome. A case of Proteus syndrome and associated findings on bone scintigraphy are presented.

Evaluation of pulmonary nodules: comparison of a prototype dual crystal (LSO/NAI) dual head coincidence camera and full ring positron emission tomography (PET).

PURPOSE: To determine the concordance of a prototype dual head coincidence camera (LSO-PS) and full ring PET (BGO-PET) using (18)F-fluorodeoxyglucose (FDG) in the evaluation of pulmonary nodules (PNs). MATERIALS AND METHODS: Patients referred for evaluation of < or =3 PNs (< or =3 cm diameter) were prospectively studied on the same day with both BGO-PET and LSO-PS. Imaging was performed at 60 and 120 min after injection of 370MBq FDG, respectively. Images were independently interpreted by four observers with each observer blinded to the other modality for the same patient. Lesions were scored in terms of relative intensity versus background. Non-attenuation corrected (nonAC) BGO-PET was used as the reference test. RESULTS: Forty-seven patients with 54 PNs (mean diameter 1.7 cm, S.D. 0.7) were included. Twelve nodules were in the < or =1.0 cm - 27 in the 1.1-2.0 cm - and 15 in the 2.1-3.0 cm range. Interobserver agreement was similar for both FDG imaging modalities. Using a sensitive assessment strategy with LSO-PS (> or = faint intensity deemed positive), there was a 97% (38/39, 95%CI 87-100%) concordance with BGO-PET and one false positive case with LSO-PS. Conservative reading (moderate or intense intensity deemed positive) resulted in a 92% (36/39, 95%CI 80-97%) concordance with BGO-PET, without false positives. The only lesion missed by LSO-PS using both assessment strategies involved a nodule 1.5 cm diameter that demonstrated moderate increased FDG uptake on BGO-PET. CONCLUSION: Depending on the test positivity criteria, LSO-PS demonstrates a high concordance (92-97%) with nonAC BGO-PET for the characterization of pulmonary nodules.

Accuracy of diagnostic imaging techniques in the diagnosis of aseptic loosening of the femoral component of a hip prosthesis: a meta-analysis.

In this meta-analysis we included 32 English-language articles published between January 1975 and June 2004 on the diagnostic performance of plain radiography, subtraction arthrography, nuclear arthrography and bone scintigraphy in detecting aseptic loosening of the femoral component, using criteria based on the Cochrane systematic review of screening and diagnostic tests. The mean sensitivity and specificity were, respectively, 82% (95% confidence interval (CI) 76 to 87) and 81% (95% CI 73 to 87) for plain radiography and 85% (95% CI 75 to 91) and 83% (95% CI 75 to 89) for nuclear arthrography. Pooled sensitivity and specificity were, respectively, 86% (95% CI 74 to 93) and 85% (95% CI 77 to 91) for subtraction arthrography and 85% (95% CI 79 to 89) and 72% (95% CI 64 to 79) for bone scintigraphy. Although the diagnostic performance of the imaging techniques was not significantly different, plain radiography and bone scintigraphy are preferred for the assessment of a femoral component because of their efficacy and lower risk of patient morbidity.

[18F]fluorodeoxyglucose uptake in recurrent thyroid cancer is related to hexokinase i expression in the primary tumor.

Patients suspected of recurrent differentiated thyroid cancer (DTC) may require "blind" (131)I therapy, with the disadvantage of unpredictable efficacy and toxicity. Alternatively, positron emission tomography (PET) with [(18)F]fluorodeoxyglucose ((18)FDG) can document the recurrence, thereby rationalizing therapeutic options. This study compared (18)FDG uptake in vivo with biomarkers expected to be involved in the underlying biological mechanisms. Additionally, we investigated whether such features were present in the primary tumors. Preoperatively, 19 patients with recurrent DTC underwent PET. (18)FDG uptake was compared with histological and immunohistochemical features in surgical specimens of recurrent and primary tumor. Thirteen of 19 recurrences were positive at PET, and (18)FDG uptake was associated with the expression of hexokinase type I (HK I; P = 0.011). All lesions with HK I overexpression were positive on (18)FDG PET. HK I expression in the original primary tumor and the metastases was similar in 82% (rho = 0.648; P = 0.005). In suspected recurrent thyroid cancer, stratification for (18)FDG PET may benefit from pretest immunohistochemical analysis of HK I of the primary tumor, as HK I negativity indicates a low likelihood of PET positivity.

In search of an unknown primary tumour presenting with extracervical metastases: the diagnostic performance of FDG-PET.

A retrospective study was carried out to determine the performance of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with unknown primary tumours presenting with metastases external to the neck. All patients referred to an academic PET centre (July, 1997 to December, 2000) presenting with an extracervical metastasis and no prior systemic therapy were eligible. The minimum follow-up period was 11 months. From 63 eligible cases, known metastases were FDG avid in all but one neuroendocrine process. PET scans were retrospectively classified as positive for a primary tumour (n=29), i.e. revealing at least one anatomical site suspected to be the primary tumour. This was confirmed in 16, either by histology (n=10) or radiological and clinical follow-up (n=6). There were four false positive cases. In nine patients, the primary tumour was never confirmed. Of the remaining 33 negative PET scans the primary tumour was clinically not found in 18. Follow-up and additional pathology investigations demonstrated the primary tumour in 15. A survey on clinical usefulness of PET (response rate 83%) suggested that PET positively contributed to diagnostic understanding in 29 of 52 evaluable cases. Applied late in the diagnostic trajectory, approximately four patients need to be scanned by PET in order to find one primary tumour. However, in addition to direct demonstration of unknown primaries, there appears to be a positive effect on the diagnostic work-up of these patients of a similar magnitude.

Effect of increased (99m)Tc/(99)Tc ratios on count rates in sentinel node procedures: a randomised study.

The aim of this study was to evaluate the count rates of sentinel lymph nodes (SLNs) in patients with breast cancer in the operating theatre, using (99m)Tc-Nanocoll with different ratios of technetium-99m to technetium-99. After written informed consent had been obtained, we tested different ratios of (99m)Tc/(99)Tc-Nanocoll in a double-blinded randomised study performed in 161 patients. Twenty-five MBq/ microg (99m)Tc-colloid albumin was prepared in vacuum. In 87 patients (group A) a 2-h elution was used and in 74 patients (group B) a 24-h elution was used. Patients were subcategorised into subgroups 1 and 3, in which an SLN procedure for breast carcinoma was performed simultaneously with lumpectomy, and subgroups 2 and 4, in which an SLN procedure was performed 2-3 weeks after prior excision biopsy. All patients were injected along the lateral border of the areola (two injections: 50 MBq/0.3 ml intradermally and 50 MBq/2 ml intraparenchymally). Ex vivo measurement of count rates was performed with a gamma probe. Comparing groups A and B in respect of registered counts per second (cps) of excised SLNs, a significant difference was found ( P<0.004). When comparisons were made between subgroups 1 and 2 (2-h elution) and between subgroups 3 and 4 (24-h elution) in respect of registered cps of excised SLNs, no significant difference was found (subgroup 1 vs 2, P=0.825; subgroup 3 vs 4, P=0.915). Use of a 2-h elution in vacuum yielded a significantly higher count rate of maximum specific activity of (99m)Tc-colloid albumin in SLNs than was achieved using a 24-h elution in vacuum. SLN procedures performed 2-3 weeks after prior excision biopsy proved reliable as compared to SLN procedures performed simultaneously with lumpectomy.