Effect of Suboccipital Release on Pain Perception and Autonomic Reflex Responses to Ischemic and Cold Pain.

OBJECTIVE/SUBJECTS: To determine the autonomic effects of suboccipital release (SOR) during experimentally induced pain, 16 healthy subjects (eight women, eight men) experienced ischemic (forearm postexercise muscle ischemia [PEMI]) and cold (cold pressor test [CPT]) pain. DESIGN: Beat-to-beat heart rate (electrocardiogram), mean arterial blood pressure (finger photoplethysmography), baroreflex sensitivity (transfer function analysis), and pain perception were measured. SOR or a sham (modified yaw; 30 cycles/min) was performed in minute 2 of pain. RESULTS: PEMI increased blood pressure by 23 ± 2 and 20 ± 2 mmHg; no differences occurred between SOR or yaw. PEMI modestly elevated heart rate during ischemia, followed by significant reduction from baseline with SOR (-3 ± 2 bpm) and yaw (-4 ± 2 bpm); no differences were observed between treatments. CPT increased blood pressure (SOR = 11 ± 1, yaw = 9 ± 2 mmHg) and heart rate (SOR = 10 ± 2, yaw = 8 ± 3 bpm) before SOR and yaw. Neither treatment nor sham blunted blood pressure increases (SOR = 25 ± 2, yaw = 22 ± 2 mmHg) during CPT; both decreased heart rate (SOR = -3 ± 2, yaw = -2 ± 2 bpm) from baseline. PEMI and CPT caused increased pain without treatment modulation. Following pain and manual intervention, SOR increased baroreflex sensitivity in the 0.15-0.35 Hz range and decreased R-R interval power spectral density in the 0.03-0.5 Hz range compared with yaw. To probe potential mechanisms and interactions between manual treatment and a prototypic analgesic, oral aspirin (967 mg) was given 60 minutes before testing to reduce prostaglandin synthesis. Aspirin slightly attenuated pain but neither altered cardiovascular changes to PEMI nor interacted with SOR or yaw. CONCLUSIONS: SOR has the capacity to modulate pain-induced autonomic control and regulation.

Maternal body mass index, smoking status and small for gestational age: an Australian retrospective cohort study.

OBJECTIVES: Both maternal body mass index (BMI) and smoking during pregnancy have been associated with a range of adverse maternal and infant birth outcomes. This study aimed to identify whether these independent variables had an interacting relationship with small for gestational age in an Australian obstetric cohort. STUDY DESIGN: A retrospective cohort design used data from the Birthing Outcomes System of a major tertiary hospital in Australia. METHODS: A total of 14,487 singleton births between January 2008 and December 2013 were included in the analysis. Chi-squared tests and one-way analysis of variance were used for the comparison of categorical and continuous variables, respectively. Adjusted odds ratios (AORs) were calculated to determine the association of smoking status with the outcome variable of interest, and these are reported for each maternal BMI category. RESULTS: Of the 14,487 women, 716 (4.9%) were underweight (BMI ≤18 kg/m2), 7268 (50.2%) had healthy weight (BMI = 19-24 kg/m2), 3658 (25.3%) were overweight (BMI = 25-29 kg/m2), 1558 (10.8%) had class I obesity (BMI = 30-34 kg/m2), 711 (4.9%) had class II obesity (BMI = 35-39 kg/m2) and 576 (3.9%) had class III obesity (BMI = 40+ kg/m2). Of all women, 10.8% reported being current smokers, 82.0% reported to have never smoked and 4.0% reported to have stopped smoking during or before pregnancy. Smokers with a BMI ≥40 kg/m2 were 4.5 (AOR = 4.508; 95% confidence interval: 2.068-9.828) times more likely to give birth to a small-for-gestational-age infant than non-smokers within the same BMI category. This increased risk was not observed in women who ceased smoking before or during pregnancy. CONCLUSIONS: Our study supports the efficacy of antismoking policies within maternal public health. In addition, greater support with respect to smoking cessation is indicated for women during pregnancy with an elevated BMI.

[What actually happens in hybrid imaging?] / Was passiert eigentlich in der Hybridbildgebung?

CLINICAL/METHODOLOGICAL ISSUE: The goal of this article is to shed light on innovations in perfusion imaging and the fields of application that have opened up in hybrid imaging of the heart. STANDARD RADIOLOGICAL METHODS: As before, the most commonly used modalities in hybrid imaging are single photon emission computed tomography (SPECT) and positron emission tomography/computed tomography (PET/CT). Perfusion tracers and the radioactively labeled glucose analog 18F­fluorodeoxyglucose (FDG) are commonly used for vitality imaging. METHODICAL INNOVATIONS: Use of PET/MRI (magnetic resonance imaging) is becoming increasingly widespread. In addition, FDG is also increasingly applied in imaging infectious and inflammatory myocardial diseases. Furthermore, novel tracers are used, such as the amyloid-specific tracers in cardiac amyloidosis. PERFORMANCE: Overall, this development has led to an increasing use of hybrid imaging techniques. These still include myocardial perfusion imaging, but are also used in inflammatory and infectious diseases such as endocarditis, myocarditis and sarcoidosis, as well as in underestimated diseases such as cardiac amyloidosis. The use of tracers has led to the creation of new fields of application in hybrid imaging. PRACTICAL RECOMMENDATIONS: Hybrid imaging combining myocardial perfusion and coronary visualization seems to be particularly advantageous in complex cases such as multivessel disease. In infectious and inflammatory myocardial diseases, FDG PET/CT or PET/MRI has clearly demonstrated its added value. New fields of application are very promising, but their significance has yet to be clearly demonstrated.

Correction to: 18F-NaF PET/CT: EANM procedure guidelines for bone imaging.

The original version of this article unfortunately contained an error. The name and affiliation of "Frédéric Paycha" needs to be corrected. Given in this article is the correct author name and affiliation.

Altered stimulus representation in rat auditory cortex is not causal for loss of consciousness under general anaesthesia.

BACKGROUND: Current concepts suggest that impaired representation of information in cortical networks contributes to loss of consciousness under anaesthesia. We tested this idea in rat auditory cortex using information theory analysis of multiunit responses recorded under three anaesthetic agents with different molecular targets: isoflurane, propofol, and dexmedetomidine. We reasoned that if changes in the representation of sensory stimuli are causal for loss of consciousness, they should occur regardless of the specific anaesthetic agent. METHODS: Spiking responses were recorded with chronically implanted microwire arrays in response to acoustic stimuli incorporating varied temporal and spectral dynamics. Experiments consisted of four drug conditions: awake (pre-drug), sedation (i.e. intact righting reflex), loss of consciousness (a dose just sufficient to cause loss of righting reflex), and recovery. Measures of firing rate, spike timing, and mutual information were analysed as a function of drug condition. RESULTS: All three drugs decreased spontaneous and evoked spiking activity and modulated spike timing. However, changes in mutual information were inconsistent with altered stimulus representation being causal for loss of consciousness. First, direction of change in mutual information was agent-specific, increasing under dexmedetomidine and decreasing under isoflurane and propofol. Second, mutual information did not decrease at the transition between sedation and LOC for any agent. Changes in mutual information under anaesthesia correlated strongly with changes in precision and reliability of spike timing, consistent with the importance of temporal stimulus features in driving auditory cortical activity. CONCLUSIONS: The primary sensory cortex is not the locus for changes in representation of information causal for loss of consciousness under anaesthesia.

Medial frontal GABA is lower in older schizophrenia: a MEGA-PRESS with macromolecule suppression study.

Gamma-butyric acid (GABA) dysfunction has been implicated in the pathophysiology of schizophrenia and its cognitive deficits. Proton magnetic resonance spectroscopy (MRS) was used to test the hypothesis that older participants with schizophrenia have lower anterior cingulate GABA levels compared with older control participants. One-hundred forty-five participants completed this study. For detection of GABA, spectra were acquired from the medial frontal/anterior cingulate cortex using a macromolecule-suppressed MEGA-PRESS sequence. Patients were evaluated for psychopathology and all participants completed neuropsychological tests of working memory, processing speed and functional capacity. GABA levels were significantly lower in the older participants with schizophrenia (n=31) compared with the older control (n=37) group (P=0.003) but not between the younger control (n=40) and schizophrenia (n=29) groups (P=0.994). Age strongly predicted GABA levels in the schizophrenia group accounting for 42% of the variance, but the effect of age was less in the control group accounting for 5.7% of the variance. GABA levels were specifically related to working memory but not processing speed performance, functional capacity, or positive or negative symptom severity. This is the largest MRS study of GABA in schizophrenia and the first to examine GABA without macromolecule contamination, a potentially significant issue in previous studies. GABA levels more rapidly declined with advancing age in the schizophrenia compared with the control group. Interventions targeted at halting the decline or increasing GABA levels may improve functional outcomes and quality of life as patients with schizophrenia age.

Disruption of cortical network activity by the general anaesthetic isoflurane.

BACKGROUND: Actions of general anaesthetics on activity in the cortico-thalamic network likely contribute to loss of consciousness and disconnection from the environment. Previously, we showed that the general anaesthetic isoflurane preferentially suppresses cortically evoked synaptic responses compared with thalamically evoked synaptic responses, but how this differential sensitivity translates into changes in network activity is unclear. METHODS: We investigated isoflurane disruption of spontaneous and stimulus-induced cortical network activity using multichannel recordings in murine auditory thalamo-cortical brain slices. RESULTS: Under control conditions, afferent stimulation elicited short latency, presumably monosynaptically driven, spiking responses, as well as long latency network bursts that propagated horizontally through the cortex. Isoflurane (0.05-0.6 mM) suppressed spiking activity overall, but had a far greater effect on network bursts than on early spiking responses. At isoflurane concentrations >0.3 mM, network bursts were almost entirely blocked, even with increased stimulation intensity and in response to paired (thalamo-cortical + cortical layer 1) stimulation, while early spiking responses were <50% blocked. Isoflurane increased the threshold for eliciting bursts, decreased their propagation speed and prevented layer 1 afferents from facilitating burst induction by thalamo-cortical afferents. CONCLUSIONS: Disruption of horizontal activity spread and of layer 1 facilitation of thalamo-cortical responses likely contribute to the mechanism by which suppression of cortical feedback connections disrupts sensory awareness under anaesthesia.

(18)F-NaF PET/CT: EANM procedure guidelines for bone imaging.

The aim of this guideline is to provide minimum standards for the performance and interpretation of (18)F-NaF PET/CT scans. Standard acquisition and interpretation of nuclear imaging modalities will help to provide consistent data acquisition and numeric values between different platforms and institutes and to promote the use of PET/CT modality as an established diagnostic modality in routine clinical practice. This will also improve the value of scientific work and its contribution to evidence-based medicine.

Liquid dextran does not increase the elution rate of different antibiotics from bone cement.

PURPOSE: To investigate the possibility of increasing elution of fosfomycin, gentamicin, clindamycin, and vancomycin by the addition of dextran fluid during the cement-mixing phase. METHODS: In 12 test series, we produced standardized, antibiotic-loaded test specimens of cement, with and without addition of dextran, and determined their effectiveness against three reference pathogens in agar diffusion and elution tests. RESULTS: In the test series using combined agents, Refobacin(®)-Palacos(®)R plus fosfomycin continuously produced the largest zone of inhibition, both against methicillin-sensitive Staphylococcus aureus (p = 0.009) and against methicillin-resistant Staphylococcus aureus (p = 0.009). The addition of dextran to the various test series had no useful effect on the size of the zone of inhibition for any of the antibiotics tested. CONCLUSIONS: Dextran supplementation in Refobacin(®)-Palacos(®)R bone cement did not have the hope for positive effect on the elution rate of bound antibiotics.

Extracellular calcium chelation and attenuation of calcium entry decrease in vivo cholinergic-induced eccrine sweating sensitivity in humans.

NEW FINDINGS: What is the central question of this study? Calcium is an important second messenger in eccrine sweating; however, whether modulation of extracellular Ca(2+) and Ca(2+) entry has the capacity to modulate sweat rate in non-glabrous human skin has not been explored. What is the main finding and its importance? Acetylcholine to sweat rate dose-response relationships identify that local in vivo Ca(2+) chelation and L-type Ca(2+) channel antagonism have the capacity to attenuate the cholinergic sensitivity of eccrine sweat glands. Importantly, these data translate previous glabrous in vitro animal studies into non-glabrous in vivo human skin. Calcium is an important second messenger in eccrine sweating, with both internal and external sources being identified in vitro. It is unclear whether in vivo modulation of extracellular Ca(2+) levels or influx has the capacity to modulate sweat rate in non-glabrous human skin. To test the hypothesis that lowering interstitial Ca(2+) levels would decrease the sensitivity of the ACh to sweat rate (via capacitance hygrometry) dose-response relationship, nine healthy subjects received six ACh doses (1 × 10(-5) to 1 × 10(0) m in 10-fold increments) with and without a Ca(2+) chelator (12.5 mg ml(-1) EDTA) via forearm intradermal microdialysis (protocol 1). To test the hypothesis that attenuating Ca(2+) influx via L-type Ca(2+) channels would also decrease the sensitivity of the ACh to sweat rate dose-response relationship, 10 healthy subjects received similar ACh doses with and without a phenylalkylamine Ca(2+) channel blocker (1 mm verapamil; protocol 2). Non-linear regression curve fitting identified a right-shifted ED50 in EDTA-treated sites compared with ACh alone (-1.0 ± 0.1 and -1.5 ± 0.1 logm, respectively; P < 0.05), but unchanged maximal sweat rate (0.60 ± 0.07 and 0.58 ± 0.11 mg cm(-2) min(-1), respectively; P > 0.05) in protocol 1. Protocol 2 also resulted in a right-shifted ED(50) (verapamil, -0.9 ± 0.1 logm; ACh alone, -1.6 ± 0.2 logm; P < 0.05), with unchanged maximal sweat rate (verapamil, 0.45 ± 0.08 mg cm(-2) min(-1); ACh alone, 0.35 ± 0.06 mg cm(-2) min(-1); P > 0.05). Thus, local in vivo Ca(2+) chelation and L-type Ca(2+) channel antagonism have the capacity to attenuate in vivo cholinergic sensitivity of eccrine sweat glands. These data suggest that interstitial Ca(2+) and its influx via Ca(2+) channels play a functional role in eccrine sweating in intact non-glabrous human skin.

[Nuclear medicine procedure guideline for sentinel lymph node localization]. / DGN-Handlungsempfehlung (S1-Leitlinie) ­ Version 3.

The authors present a procedure guideline for scintigraphic detection of sentinel lymph nodes in malignant melanoma, in breast cancer, in penile and vulva tumors, in head and neck cancer, and in prostate carcinoma. Important goals of sentinel lymph node scintigraphy comprise reduction of the extent of surgery, lower postoperative morbidity and optimization of histopathological examination focussing on relevant lymph nodes. Sentinel lymph node scintigraphy itself does not diagnose tumorous lymph node involvement and is not indicated when lymph node or distant metastases have been definitely diagnosed before sentinel lymph node scintigraphy. Procedures are compiled with the aim to reliably localise sentinel lymph nodes with a high detection rate typically in early tumour stages. New aspects in this guideline are new radiopharmaceuticals such as tilmanocept and Tc-99m-PSMA and SPECT/CT allowing an easier anatomical orientation. Initial dynamic lymphoscintigraphy in breast cancer is of little significance nowadays. Radiation exposure is low so that pregnancy is not a contraindication for sentinel lymph node scintigraphy. A one-day protocol should preferentially be used. Even with high volumes of scintigraphic sentinel lymph node procedures surgeons, theatre staff and pathologists receive a radiation exposure < 1 mSv/year so that they do not require occupational radiation surveillance. Aspects of quality control were included (scintigraphy, quality control of gamma probe, 6 h SLN course for surgeons, certified breast centers, medical surveillance center).

Role of choline PET/CT in guiding target volume delineation for irradiation of prostate cancer.

Choline PET/CT has shown limitations for the detection of primary prostate cancer and nodal metastatic disease, mainly due to limited sensitivity and specificity. Conversely in the restaging of prostate cancer recurrence, choline PET/CT is a promising imaging modality for the detection of local regional and nodal recurrence with an impact on therapy management. This review highlights current literature on choline PET/CT for radiation treatment planning in primary and recurrent prostate cancer. Due to limited sensitivity and specificity in differentiating between benign and malignant prostatic tissues in primary prostate cancer, there is little enthusiasm for target volume delineation based on choline PET/CT. Irradiation planning for the treatment of single lymph node metastases on the basis of choline PET/CT is controversial due to its limited lesion-based sensitivity in primary nodal staging. In high-risk prostate cancer, choline PET/CT might diagnose lymph node metastases, which potentially can be included in the conventional irradiation field. Prior to radiation treatment of recurrent prostate cancer, choline PET/CT may prove useful for patient stratification by excluding distant disease which would require systemic therapy. In patients with local recurrence, choline PET/CT can be used to delineate local sites of recurrence within the prostatic resection bed allowing a boost to PET-positive sites. In patients with lymph node metastases outside the prostatic fossa and regional metastatic lymph nodes, choline PET/CT might influence radiation treatment planning by enabling extension of the target volume to lymphatic drainage sites with or without a boost to PET-positive lymph nodes. Further clinical randomized trials are required to assess treatment outcomes following choline-based biological radiation treatment planning in comparison with conventional radiation treatment planning.

Conceptual basis for prescriptive growth standards from conception to early childhood: present and future.

BACKGROUND: Healthy growth in utero and after birth is fundamental for lifelong health and wellbeing. The World Health Organization (WHO) recently published standards for healthy growth from birth to 6 years of age; analogous standards for healthy fetal growth are not currently available. Current fetal growth charts in use are not true standards, since they are based on cross-sectional measurements of attained size under conditions that do not accurately reflect normal growth. In most cases, the pregnant populations and environments studied are far from ideal; thus the data are unlikely to reflect optimal fetal growth. A true standard should reflect how fetuses and newborns 'should' grow under ideal environmental conditions. OBJECTIVE: The development of prescriptive intrauterine and newborn growth standards derived from the INTERGROWTH-21(st) Project provides the data that will allow us for the first time to establish what is 'normal' fetal growth. METHODS: The INTERGROWTH-21(st) study centres provide the data set obtained under pre-established standardised criteria, and details of the methods used are also published. DESIGN: Multicentre study with sites in all major geographical regions of the world using a standard evaluation protocol. RESULTS: These standards will assess risk of abnormal size at birth and serve to evaluate potentially effective interventions to promote optimal growth beyond securing survival. DISCUSSION: The new normative standards have the potential to impact perinatal and neonatal survival and beyond, particularly in developing countries where fetal growth restriction is most prevalent. They will help us identify intrauterine growth restriction at earlier stages of development, when preventive or corrective strategies might be more effective than at present. CONCLUSION: These growth standards will take us one step closer to effective action in preventing and potentially reversing abnormal intrauterine growth. Achieving 'optimal' fetal growth requires that we act not only during pregnancy but that we optimize the maternal uterine environment from the time before conception, through embryonic development until fetal growth is complete. The remaining challenge is how 'early' will we be able to act, now that we can better monitor fetal growth.

Alterations in peak ground-reaction force during 60-cm drop landings caused by a single session of repeated Wingate anaerobic tests.

CONTEXT: Lower extremity injury is prevalent among individuals participating in sports. Numerous variables have been reported as predisposing risk factors to injury; however, the effects of muscle fatigue on landing kinetics are unclear. OBJECTIVES: To investigate the effects of a single session of repeated muscle fatigue on peak vertical ground-reaction force (GRF) during drop landings. DESIGN: Mixed factorial with repeated measures. SETTING: Controlled laboratory. PARTICIPANTS: 10 female and 10 male healthy recreational athletes. INTERVENTION: Subjects performed 3 fatigued drop landings (60 cm) after four 20-s Wingate anaerobic tests (WATs) with 5 min of active recovery between fatigued conditions. MAIN OUTCOME MEASURES: Kinetic data of peak forefoot (F1) force, peak rear-foot (F2) force, and anteroposterior (AP) and mediolateral (ML) forces at both F1 and F2. RESULTS: A significant main effect was observed in the nonfatigued and fatigued drop landings in respect to peak F2 force. The greatest significant difference was shown between the first fatigued drop-landing condition and the last fatigued drop-landing condition. No significant difference was observed between genders for all GRF variables across fatigue conditions. CONCLUSION: A single session of repeated conditions of anaerobic muscle fatigue induced by WATs caused an initial reduction in peak F2 force followed by an increase in peak F2 force across conditions. Muscle fatigue consequently alters landing kinetics, potentially increasing the risk of injury.

Sustained renal response to mycophenolate mofetil and CNI taper promotes survival in liver transplant patients with CNI-related renal dysfunction.

AIM: The aim of this trial was to evaluate the impact of conversion from a calcineurin-inhibitor (CNI)-based immunosuppressive regimen to mycophenolate mofetil (MMF) and reduced-dose CNI on long-term renal function and survival in a series of 63 liver transplant patients with CNI-induced renal dysfunction. METHODS: CNI dosage was significantly tapered after introduction of 2,000 mg MMF per day. Renal function was assessed by determination of serum creatinine levels and calculated creatinine clearance (CCl). The impact of relevant clinical parameters on renal function and survival post-conversion was analyzed by univariate and multivariate analysis. RESULTS: At 60 months post-conversion, mean creatinine level had significantly declined from 197.2±58.3 µmol/l at baseline to 160.0±76.5 µmol/l, and mean CCl has significantly increased from 38.4±13.4 ml/min at baseline to 47.9±21.1 ml/min (p<0.001), respectively. Forty-six patients (73.1%) demonstrated sustained renal response to modified immunosuppression. Full-dose MMF medication (p=0.006) and the early conversion (p=0.02) were identified as independent predictors of persistent renal function improvement. Sustained renal response to MMF plus reduced-dose CNI was identified as the most relevant independent promoter of long-term survival (hazard ratio 6.9). Five-year survival rate post-conversion was 93.9% in renal responders and 64.3% in renal non-responders (log rank<0.001). CONCLUSIONS: Sustained renal response to MMF and CNI dose reduction promotes long-term survival in liver transplant patients with CNI-induced renal dysfunction.

[German guidelines for brain tumour imaging by PET and SPECT using labelled amino acids]. / PET- und SPECT-Untersuchungen von Hirntumoren mit radioaktiv markierten Aminosäuren.

For the primary diagnosis of brain tumours, morphological imaging by means of magnetic resonance imaging (MRI) is the current method of choice. The complementary use of functional imaging by positron emitting tomography (PET) and single photon emitting computerized tomography (SPECT) with labelled amino acids can provide significant information on some clinically relevant questions, which are beyond the capacity of MRI. These diagnostic issues affect in particular the improvement of biopsy targeting and tumour delineation for surgery and radiotherapy planning. In addition, amino acid labelled PET and SPECT tracers are helpful for the differentiation between tumour recurrence and non-specific post-therapeutic tissue changes, in predicting prognosis of low grade gliomas, and for metabolic monitoring of treatment response. The application of dynamic PET examination protocols for the assessment of amino acid kinetics has been shown to enable an improved non-invasive tumour grading. The purpose of this guideline is to provide practical assistance for indication, examination procedure and image analysis of brain PET/SPECT with labelled amino acids in order to allow for a high quality standard of the method. After a short introduction on pathobiochemistry and radiopharmacy of amino acid labelled tracers, concrete and detailed information is given on the several indications, patient preparation and examination protocols as well as on data reconstruction, visual and quantitative image analysis and interpretation. In addition, possible pitfalls are described, and the relevant original publications are listed for further information.

New trends for staging and therapy for localized gastroesophageal cancer: the role of PET.

Treatment options for localized gastroesophageal cancers reach from limited resection to multimodality treatment. Accurate clinical assessment, prognostic and predictive information are needed to select the most appropriate treatment approach. Positron emission tomography (PET) in combination with computed tomography (CT) in a hybrid imaging modality PET-CT may refine the staging accuracy and add prognostic information. Moreover, experiences from diverse centers indicate that PET also might improve significantly the assessment of response to preoperative chemotherapy and chemoradiotherapy. This article outlines the current value of PET in the staging and multidisciplinary care of gastroesophageal cancer. At this stage, it remains unclear whether the prognosis of patients can be improved by implementing PET in the management of localized disease. Prospective multicenter studies have to be carried out to validate metabolic cut-off values and to prove the benefit of PET-guided treatment decisions.

[Tracers in oncology - preclinical and clinical evaluation]. / Innovative Tracer in der onkologischen Diagnostik. Präklinische und klinische Evaluierung.

UNLABELLED: In oncology, PET and PET/CT with tracers beyond FDG target more specific biological processes, such as proliferation (18F-3´-fluoro-3´-deoxy-L-thymidine; 18F-FLT), tumour hypoxia (18F-fluoromisonidazol; 18F-FMISO) and phospholipid metabolism (radioactively labelled choline derivates). FLT is a thymidine analogue which can be labelled with 18F. PET with 18F-FLT enables to non-invasively image and to quantify the proliferation fraction of tumours. Proliferation dependent accumulation of FLT has been demonstrated for a variety of solid and haematologic neoplasms including lung cancer, breast cancer, gastric cancer, colorectal cancer and malignant lymphoma. Furthermore, FLT has been suggested as surrogate marker for the assessment of response to treatment, especially when targeted drugs are utilized. PET imaging in particular has emerged as a promising non-invasive tool to accurately characterize tumour oxygenation. The great promise of PET/CT is its potential as a single imaging modality for whole body staging that provides anatomical and biological information on the disease as a whole. It allows a more precise estimation of the hypoxic tumour volume as well as comparisons on a voxel-by-voxel basis (parametric mapping). PET and PET/CT with hypoxia tracers thus offer the potential to optimize and individualize therapy for patients suffering from cancer. PET- and PET/CT-studies using 11C- or 18F-labeled choline derivates recently have shown promising results for re-staging prostate cancer in patients with biochemical recurrence and advanced prostate cancer. In patients with biochemical recurrence of prostate cancer after primary therapy the detection rate of 11C-choline-PET/CT shows a positive relationship with serum PSA-levels. In these patients 11C-choline PET/CT allows not only to diagnose but also to localize recurrent disease with implications on disease management (localised vs. systemic therapy). CONCLUSION: The clinical success of multimodal imaging with PET/CT is expected to promote the combination of MRI and PET in the future.

[Bone scanning with sodium 18F-fluoride PET and PET/CT. German guideline Version 1.0.]. / Skelettdiagnostik mittels 18F-Natriumfluorid-PET und -PET/CT. DGN-Leitlinie Version 1.0.

In nuclear medicine, bone scanning is based on the principle of scintigraphy using bone-seeking radiopharmaceuticals which accumulate in sites of increased bone formation. From a historical point of view, (18)F-fluoride was one of the first osteotropic tracers which was replaced by (99m)Tc-labelled polyphosphonates. With the development of modern PET equipment the superior diagnostic performance of (18)F-fluoride PET for the detection and characterization of osseous lesions was proven in comparison to conventional bone scanning. Recently, its importance as a substitute of conventional skeletal scintigraphy increased in a time with limited availability of (99)Mo/(99m)Tc. To ensure health care during this period, (18)F-fluoride PET currently became part of common outpatient care. This guideline comprehends recommendations on indications, protocols, interpretation and reporting of (18)F-fluoride PET and PET/CT.

Lesion concordance, image quality and artefacts in PET/CT: results of a multicenter study.

AIM: This study had three major objectives: 1.) to record the number of concordant (both in PET and CT) pathological lesions in different body regions/organs, 2.) to evaluate the image quality and 3.) to determine both, the quantity and the quality of artefacts in whole body FDG PET/CT scans. PATIENTS, METHODS: Routine whole body scans of 353 patients referred to FDG-PET/CT exams at 4 university hospitals were employed. All potentially malignant lesions in 13 different body regions/organs were classified as either concordant or suspicious in FDG-PET or CT only. In the latter case the diagnostic relevance of this disparity was judged. The image quality in PET and CT was rated as a whole and separately in 5 different body regions. Furthermore we investigated the frequency and site of artefacts caused by metal implants and oral or intravenous contrast media as well as the subjective co-registration quality (in 4 body regions) and the diagnostic impact of such artefacts or misalignment. In addition, the readers rated the diagnostic gain of adding the information from the other tomographic method. RESULTS: In total 1941 lesions (5.5 per patient) were identified, 1094 (56%) out of which were concordant. 602 (71%) out of the 847 remaining lesions were detected only with CT, 245 (29%) were only PET-positive. As expected, CT particularly depicted the majority of lesions in the lungs and abdominal organs. However, the diagnostic relevance was greater with PET-only positive lesions. Most of the PET/CT scans were performed with full diagnostic CT including administration of oral and intravenous contrast media (> 80%). The image quality in PET and CT was rated excellent. Artefacts occurred in more than 60% of the scans and were mainly due to (dental) metal implants and contrast agent. Nevertheless there was almost no impact on diagnostic confidence if reading of the non attenuation corrected PET was included. The co-registration quality in general was also rated as excellent. Misalignment mostly occurred due to patient motion and breathing and led to diagnostic challenges in about 4% of all exams. The diagnostic gain of adding PET to a CT investigation was rated higher than vice versa. CONCLUSIONS: As the image quality in both PET and CT was more than satisfying, CT-artefacts almost never led to diagnostic uncertainties and serious misalignment rarely occurred, PET/CT can be considered as suitable for routine use and may replace single PET- and CT-scans. However, additional reading of the non attenuation corrected PET is mandatory to assure best possible diagnostic confidence in PET. Since approximately half of all lesions found in PET/CT were not concordant, at least in a setting with a diagnostic CT the exams need to be reported by both a nuclear medicine physician and a radiologist in consensus.