Polarized thermal emission from dust in a galaxy at redshift 2.6.

Magnetic fields are fundamental to the evolution of galaxies, playing a key role in the astrophysics of the interstellar medium and star formation. Large-scale ordered magnetic fields have been mapped in the Milky Way and nearby galaxies1,2, but it is not known how early in the Universe such structures formed3. Here we report the detection of linearly polarized thermal emission from dust grains in a strongly lensed, intrinsically luminous galaxy that is forming stars at a rate more than 1,000 times that of the Milky Way at redshift 2.6, within 2.5 Gyr of the Big Bang4,5. The polarized emission arises from the alignment of dust grains with the local magnetic field6,7. The median polarization fraction is of the order of 1%, similar to nearby spiral galaxies8. Our observations support the presence of a 5-kiloparsec-scale ordered magnetic field with a strength of around 500 µG or lower, oriented parallel to the molecular gas disk. This confirms that such structures can be rapidly formed in galaxies, early in cosmic history.

18F-FDG PET-CT uptake is a feature of both normal diameter and aneurysmal aortic wall and is not related to aneurysm size.

PURPOSE: Aortic metabolic activity is suggested to correlate with presence and progression of aneurysmal disease, but has been inadequately studied. This study investigates the 2-[(18)F] fluoro-2-deoxy-D-glucose ((18)F-FDG) uptake in a population of infra-renal abdominal aortic aneurysms (AAA), compared to a matched non-aneurysmal control group. METHODS: The Positron Emission Tomography - Computed Tomography (PET/CT) database was searched for infra-renal AAA. Exclusion criteria were prior repair, vasculitis, and saccular/mycotic thoracic or thoraco-abdominal aneurysms. Matching of 159 non-aneurysmal (<3 cm diameter) controls from the same population was assessed. Infra-renal aortic wall FDG uptake was assessed using visual analysis; maximum standardized uptake value (SUVmax) and target to background mediastinal blood pool ratio (TBR) were documented. Predictors of FDG uptake (age, sex, aortic diameter, hypertension, statin use, and diabetes) were assessed using univariate analysis. Follow-up questionnaires were sent to referring clinicians. RESULTS: Aneurysms (n = 151) and controls (n = 159) were matched (p > 0.05) for age, sex, diabetes, hypertension, smoking status, statin use, and indication for PET/CT. Median aneurysm diameter was 5.0 cm (range 3.2-10.4). On visual analysis there was no significant difference in the overall numbers with increased visual uptake 24% (36/151) in the aneurysm group vs. 19% (30/159) in the controls, p = ns. SUVmax was slightly lower in the aneurysm group vs. controls (mean (2 SD) 1.75(0.79) vs. 1.84(0.58), p = 0.02). However there was no difference in TBR between the AAA group and controls (mean (2 SD) 1.03 (0.46) vs. 1.05(0.31), p = 0.36). During a median 18 (interquartile range 8-35) months' follow-up 20 were repaired and four were confirmed ruptured. CONCLUSIONS: The level of metabolic activity as assessed by (18)F-FDG PET/CT in infra-renal AAA does not correlate with aortic size and does not differ between aneurysms and matched controls.

Correlation between Ki-67 immunohistochemistry and 18F-fluorothymidine uptake in patients with cancer: A systematic review and meta-analysis.

BACKGROUND: Positron emission tomography (PET) imaging using the radiotracer 18F-Fluorothymidine (FLT) has been proposed as an imaging biomarker of tumour proliferation. If FLT-PET can be established as such it will provide a non-invasive, quantitative measurement of tumour proliferation across the entire tumour. Results from validation studies have so far been conflicting with some studies confirming a good correlation between FLT uptake and Ki-67 score and others presenting negative results. METHODS: Firstly we performed a systematic review of published studies between 1998 and 2011 that explored the correlation between FLT uptake and Ki-67 score and examined possible variations in the methods used. Studies were eligible if they: (a) included patients with cancer, (b) investigated the correlation between Ki-67 measured by immunohistochemistry and FLT uptake measured with PET scanning, and (c) were published as a full paper in a peer-reviewed scientific journal. Secondly a meta-analysis of the correlation coefficient values reported from each study was performed. Correlation coefficient (r) values were extracted from each study and 95% confidence intervals (CIs) were calculated after applying Fisher's z transformation. For subgroup analysis, studies were classified by the index used to characterise Ki-67 expression (average or maximum expression), the nature of the sample (whole specimen or biopsy) and the cancer type. FINDINGS: Twenty-seven studies were identified as eligible for the meta-analysis. In the studies we examined there were variations in aspects of the methods and reporting. The meta-analysis showed that given an appropriate study design the FLT/Ki-67 correlation is significant and independent of cancer type. Specifically subgroup analysis showed that FLT/Ki-67 correlation was high in studies measuring the Ki-67 average expression regardless of use of surgery or biopsy samples (r=0.70, 95% CI=0.43-0.86, p<0.001). Of the studies that measured Ki-67 maximum expression, only those that used the whole surgical specimen provided a significant r value (r=0.72, 95% CI=0.54-0.84, p<0.001). Studies that used biopsy samples for Ki-67 maximum measurements did not produce a significant r value (r=0.04, 95% CI=-0.18-0.26, p=0.71). In terms of the cancer type subgroup analysis there is sufficient data to support a strong FLT/Ki-67 correlation for brain, lung and breast cancer. No publication bias was detected. INTERPRETATION: This systematic review and meta-analysis highlights the importance of the methods used in validation studies comparing FLT-PET imaging with the biomarker Ki-67. The correlation is significant and independent of cancer type provided a study design that uses Ki-67 average measurements, regardless of nature of sample, or whole surgical samples when measuring Ki-67 maximum expression. Sufficient data to support a strong correlation for brain, lung and breast cancer exist. However, larger, prospective studies with improved study design are warranted to validate these findings for the rest of the cancer types.

The challenges of integrating molecular imaging into the optimization of cancer therapy.

We review novel, in vivo and tissue-based imaging technologies that monitor and optimize cancer therapeutics. Recent advances in cancer treatment centre around the development of targeted therapies and personalisation of treatment regimes to individual tumour characteristics. However, clinical outcomes have not improved as expected. Further development of the use of molecular imaging to predict or assess treatment response must address spatial heterogeneity of cancer within the body. A combination of different imaging modalities should be used to relate the effect of the drug to dosing regimen or effective drug concentration at the local site of action. Molecular imaging provides a functional and dynamic read-out of cancer therapeutics, from nanometre to whole body scale. At the whole body scale, an increase in the sensitivity and specificity of the imaging probe is required to localise (micro)metastatic foci and/or residual disease that are currently below the limit of detection. The use of image-guided endoscopic biopsy can produce tumour cells or tissues for nanoscopic analysis in a relatively patient-compliant manner, thereby linking clinical imaging to a more precise assessment of molecular mechanisms. This multimodality imaging approach (in combination with genetics/genomic information) could be used to bridge the gap between our knowledge of mechanisms underlying the processes of metastasis, tumour dormancy and routine clinical practice. Treatment regimes could therefore be individually tailored both at diagnosis and throughout treatment, through monitoring of drug pharmacodynamics providing an early read-out of response or resistance.

Establishment of a UK-wide network to facilitate the acquisition of quality assured FDG-PET data for clinical trials in lymphoma.

BACKGROUND: Multicentre trials are required to determine how [fluorine-18]-2-fluoro-2-deoxy-D-glucose-positron emission tomography imaging can guide cancer treatment. Consistency in quality control (QC), scan acquisition and reporting is mandatory for high-quality results, which are comparable across sites. METHODS: A national positron emission tomography (PET) clinical trials network (CTN) has been set up with a 'core laboratory' to coordinate QC and interpret scans. The CTN is involved in trials in Hodgkin's lymphoma [Randomised Phase III trial to determine the role of FDG-PET Imaging in Clinical Stages IA/IIA Hodgkin's Disease (RAPID) and Randomised Phase III trial to assess response adapted therapy using FDG-PET imaging in patients with newly diagnosed, advanced Hodgkin lymphoma (RATHL)] and diffuse large B-cell lymphoma [Blinded evaluation of prognostic value of FDG-PET after 2 cycles of chemotherapy in diffuse large B-cell Non-Hodgkins Lymphoma, a sub-study of the R-CHOP-21 vs R-CHOP-14 trial (R-CHOP PET substudy)]. Approval to join requires scanner validation and agreement to follow a standard QC protocol. Scans are transferred to the core laboratory and reported centrally according to predetermined criteria. RESULTS: The qualification procedure was carried out on 15 scanners. All scanners were able to demonstrate the necessary quantitative accuracy, and following modification of image reconstruction where necessary, scanners demonstrated comparable recovery coefficients (RCs) indicating similar performance. The average RC (±1 standard deviation) was 0.56 ± 0.095 for the 13-mm sphere. Reports from 444 of 473 (94%) patients in RAPID and 67 of 73 (92%) patients in RATHL were available for randomisation of therapy. CONCLUSIONS: The CTN has enabled consistent quality assured PET results to be obtained from multiple centres in time for clinical decision making. The results of trials will be significantly strengthened by this system.

Diabetes and bone: advantages and limitations of radiological, radionuclide and hybrid techniques in the assessment of diabetic foot.

A common cause of morbidity and mortality in diabetic patients are foot infection/complications often leading to amputation of lower extremities. Various radiological and radionuclide techniques are available for the assessment of diabetic patients with bone or soft tissue infections. However, there are several advantages and limitations. The major limitation of all these techniques is their inability to accurately differentiate osteomyelitis from charcot's/neuropathic joints. Radiologically, magnetic resonance imaging (MRI) is the technique of choice and a radiolobeled white cell scan is a useful nuclear medicine technique in the evaluation of diabetic patients with suspected foot infection. In this review we discuss the efficacy of radiological and radionuclide techniques in the assessment of diabetic foot infection.

Do atmospheric pressure changes influence seizure occurrence in the epilepsy monitoring unit?

In a prior study of epilepsy and atmospheric pressure, we were able to show a small association between changes in atmospheric pressure and increased seizure frequency in consecutive patients with epilepsy undergoing video telemetry. In this study, we used a larger data set of similar patients undergoing telemetry at another Seattle institution, and examined the possible impact of atmospheric pressure (AP) changes on seizure onset in subtypes of seizures (focal, generalized, and nonepileptic). Comparisons were made between AP score at time of seizure onset and AP score at selected time ranges prior to the event (hour of seizure and 3, 6, and 24 hours prior) and a random sample of AP scores collected over similar time frames using nonparametric testing with correction for multiple comparisons. We could find no evidence to suggest atmospheric pressure changes made seizure occurrence more likely in any of the seizure groups across any of the time periods.

Regression of melanoma metastases following treatment with the n-bisphosphonate zoledronate and localised radiotherapy.

We report a case of regression of pulmonary and bony metastases in a patient with malignant melanoma following palliative treatment with systemic zoledronate and localised radiotherapy to the bone. Zoledronate is a potent new bisphosphonate used for the treatment of metabolic bone diseases including bone metastases due to its inhibitory effect on osteoclasts. In the context of metastatic cancer zoledronate is routinely used to improve bone pain and reduce the frequency of skeletal events. There is also an increasing body of evidence suggesting that bisphosphonates exhibit anti-tumour properties. Bisphosphonates are able to activate Vgamma9Vdelta2 gamma-delta T cells which can be key players in the immune defence against malignant cells. Furthermore bisphosphonates have direct anti-proliferative, anti-metastatic and pro-apoptotic effects on tumour cells. These actions, together with their low side effect profile, may prove to be useful therapeutic tools in the treatment of cancer even in the absence of bone metastases. On the basis of this case report we here review the current literature on present preclinical and clinical studies using bisphosphonates for the treatment of cancer.

Measurement of the internal dose to families of outpatients treated with 131I for hyperthyroidism.

OBJECTIVE: The aim of this study was to measure the internal dose received by family members from ingestion of radioactive contamination after outpatient therapy. MATERIALS AND METHODS: Advice was given to minimise transfer of radioiodine. Home visits were made approximately 2, 7 and 21 days after treatment to measure radioactivity in the thyroids of family members. A decay correction was applied to radioactivity detected assuming ingestion had occurred at the earlier contact time, either the day of treatment or the previous home visit. An effective half-life of 6 or 7 days was used depending on age. Thyroid activity was summed if activity was found at more than one visit in excess of the amount attributable to radioactive decay. Effective dose (ED) was calculated using ICRP72. RESULTS AND DISCUSSION: Fifty-three adults and 92 children, median age 12 (range 4-17) years participated. Median administered activity was 576 (range 329-690) MBq (131)I. Thyroid activity ranged from 0 to 5.4 kBq in the adults with activity detected in 17. Maximum adult ED was 0.4 mSv. Thyroid activity ranged from 0 to 11.8 kBq in the children with activity detected in 26. The two highest values of 5.0 and 11.8 kBq occurred in children aged 5 and 14 years from different families. Eighty-five children had no activity or <1 kBq detected. ED was <0.2 mSv in 86 out of 92 children (93%). Previous published data showed 93% of children received an ED

Imaging neuroendocrine tumours with radionuclide techniques.

Neuroendocrine tumours (NETs) are a rare type of tumour that can range from well differentiated slow growing tumours to poorly differentiated aggressive tumours. NETs can arise in different parts of the body. Patients often present with a large spectrum of clinical syndromes, which depend on the presence of hormones secreted by the tumour type or by a mass effect. Several imaging modalities are used in the diagnosis of NETs. Radionuclide imaging plays an important role in diagnosis, staging and treatment of these tumours. Several radiopharmaceuticals are used to image NETs and are based on different cellular uptake mechanisms. This review will focus on the functional imaging of NETs using single photon emission computed tomography and positron emission tomography radiopharmaceuticals.

The role of sentinel lymph node biopsy in patients with differentiated thyroid carcinoma.

AIM: To evaluate the "state of art" of clinical role of sentinel lymph node (SLN) biopsy procedure in patients affected by differentiated thyroid carcinoma. METHODS: All papers cited on PubMed/MEDLINE until June 2005, published in English, and referred to the key words "sentinel lymph node biopsy" AND "thyroid carcinoma" OR "thyroid cancer" were reviewed for the purpose of the present study. RESULTS: The first method used for SLN biopsy in thyroid carcinoma patients was the vital blue dye technique. This technique had some disadvantages as: (a) risk of disruption of the lymphatic channels deriving from the thyroid cancer; (b) difficulty in disclosing SLN lying outside the central compartment; (c) parathyroid glands can take up blue dye and, thus, can be misinterpreted as lymph nodes. Some of the above cited disadvantages were overcome by using the lymphoscintigraphy and intraoperative gamma probe technique. A combination of the blue dye and gamma probe technique has also been proposed with synergic results. CONCLUSION: The reported advantages of the SLN biopsy in small differentiated thyroid carcinoma patients can be resumed as follows: (a) better selection of patients who would benefit from compartment oriented nodal dissection; (b) more accurate lymph node staging; (c) better selection of patients who can require (131)I treatment after surgery (SLN positive for metastasis); (d) better identification of SLN located out of the central compartment.

Use of imaging in the management of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an increasingly prevalent tumour. The death rate associated with MPM is predicted to peak in the next 10 years, although radiologists and clinicians will be encountering cases for the next few decades. Contrast-enhanced CT is an established technique for evaluating suspected malignant pleural disease, but MPM can be reliably diagnosed only by histological sampling. However, even with adequate sampling and the use of immunocytochemistry, histological diagnosis is known to be difficult; definitive diagnosis may involve a combination of clinical presentation, radiological and histological appearances. Percutaneous biopsy is a promising technique for sampling the pleura. In view of its pattern of growth, MPM is a challenging disease to image by any method, and it behaves quite differently from lung cancer. This review aims to highlight the practical aspects of assessing malignant pleural mesothelioma.

FDG-PET after two to three cycles of chemotherapy predicts progression-free and overall survival in high-grade non-Hodgkin lymphoma.

BACKGROUND: Less than 50% of all high-grade non-Hodgkin lymphoma (NHL) patients experience lasting disease-free survival. Risk-adapted treatment strategies require better tools for prediction of outcome. This investigation aimed to assess the value of positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) after two to three cycles of chemotherapy for prediction of progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS: One hundred and twenty-one patients with high-grade NHL underwent FDG-PET. The therapy response on FDG-PET was correlated to PFS and OS using Kaplan-Meier survival analysis. Cox regression analyses were employed to test for independence of known pretreatment prognostic factors. RESULTS: Fifty FDG-PET scans were negative, 19 scans showed minimal residual uptake (MRU), and 52 scans were positive. The estimated 5 year PFS was 88.8% for the PET-negative group, 59.3% for the MRU group, and 16.2% for the PET-positive group. Kaplan-Meier analyses showed strong associations between FDG-PET results and PFS (P <0.0001) and OS (P <0.01). Early interim FDG-PET was independent of the other prognostic factors. CONCLUSIONS: Early interim FDG-PET is an accurate and independent predictor of PFS and OS. An early assessment of chemotherapy response with FDG-PET could provide the basis for selection of patients for alternative therapeutic strategies.

Reading impairment in the neuronal migration disorder of periventricular nodular heterotopia.

OBJECTIVE: To define the behavioral profile of periventricular nodular heterotopia (PNH), a malformation of cortical development that is associated with seizures but reportedly normal intelligence, and to correlate the results with anatomic and clinical features of this disorder. METHODS: Ten consecutive subjects with PNH, all with epilepsy and at least two periventricular nodules, were studied with structural MRI and neuropsychological testing. Behavioral results were statistically analyzed for correlation with other features of PNH. RESULTS: Eight of 10 subjects had deficits in reading skills despite normal intelligence. Processing speed and executive function were also impaired in some subjects. More marked reading difficulties were seen in subjects with more widely distributed heterotopia. There was no correlation between reading skills and epilepsy severity or antiepileptic medication use. CONCLUSION: The neuronal migration disorder of periventricular nodular heterotopia is associated with an impairment in reading skills despite the presence of normal intelligence.

The impact of PET scanning on management of paediatric oncology patients.

PURPOSE: Limited information is available on the use of positron emission tomography (PET) in paediatric oncology. The aim of this study was to review the impact of PET on the management of paediatric patients scanned over a 10-year period. METHODS: One hundred and sixty-five consecutive oncology patients aged 11 months to 17 years were included. Two hundred and thirty-seven scans were performed. Diagnoses included lymphoma (60 patients), central nervous system (CNS) tumour (59), sarcoma (19), plexiform neurofibroma with suspected malignant change (13) and other tumours (14). A questionnaire was sent to the referring clinician to determine whether the PET scan had altered management and whether overall the PET scan was thought to be helpful. RESULTS: One hundred and eighty-nine (80%) questionnaires for 126 patients were returned (63 relating to lymphoma, 62 to CNS tumours, 30 to sarcoma, 16 to plexiform neurofibroma and 18 to other tumours). PET changed disease management in 46 (24%) cases and was helpful in 141 (75%) cases. PET findings were verified by histology, clinical follow-up or other investigations in 141 cases (75%). The returned questionnaires indicated that PET had led to a management change in 20 (32%) lymphoma cases, nine (15%) CNS tumours, four (13%) sarcomas, nine (56%) plexiform neurofibromas and four (22%) cases of other tumours. PET was thought to be helpful in 47 (75%) lymphoma cases, 48 (77%) CNS tumours, 24 (80%) sarcomas, 11 (69%) neurofibromas and 11 (61%) cases of other tumours. PET findings were verified in 44 (70%) lymphoma cases, 53 (85%) CNS tumours, 21 (70%) sarcomas, 12 (75%) neurofibromas and 11 (61%) other tumour cases. CONCLUSION: PET imaging of children with cancer is accurate and practical. PET alters management and is deemed helpful (with or without management change) in a significant number of patients, and the results are comparable with the figures published for the adult oncology population.

Chondrogenic and adipogenic potential of microvascular pericytes.

BACKGROUND: Previous studies have shown that pericytes can differentiate into osteoblasts and form bone. This study investigated whether pericytes can also differentiate into chondrocytes and adipocytes. METHODS AND RESULTS: Reverse transcription-polymerase chain reaction demonstrated that pericytes express mRNA for the chondrocyte markers Sox9, aggrecan, and type II collagen. Furthermore, when cultured at high density in the presence of a defined chondrogenic medium, pericytes formed well-defined pellets comprising cells embedded in an extracellular matrix rich in sulfated proteoglycans and type II collagen. In contrast, when endothelial cells were cultured under the same conditions, the pellets disintegrated after 48 hours. In the presence of adipogenic medium, pericytes but not endothelial cells expressed mRNA for peroxisome proliferator-activated receptor-gamma2 (an adipocyte-specific transcription factor) and incorporated lipid droplets that stained with oil red O. To confirm that pericytes can differentiate along the chondrocytic and adipocytic lineages in vivo, these cells were inoculated into diffusion chambers and implanted into athymic mice for 56 days. Accordingly, mineralized cartilage, fibrocartilage, and a nonmineralized cartilaginous matrix with lacunae containing chondrocytes were observed within these chambers. Small clusters of cells that morphologically resembled adipocytes were also identified. CONCLUSIONS: These data demonstrate that pericytes are multipotent cells that may contribute to growth, wound healing, repair, and/or the development and progression of various pathological states.