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A-0412 Ultrasonographic evaluation of theflexor tendons in function of volar platepositioning and pronator quadratus repairon cadaveric modelsChul Ki Goorens1,2, Kjell Van Royen2, Stephane Grysseels2,Steven Provyn 3, Johan De Mey2, Thierry Scheerlinck2,Jean Goubau2(1) Regionaal Ziekenhuis Tienen, Tienen, Belgium(2) University Hospital Brussels, Brussels, Belgium(3) Vrije Universiteit Brussel, Brussels, BelgiumFlexor tendon injury is a potential complication aftervolar plating of distal radius fracture due to the frictionof the flexor tendons and the prominence of thevolar plate. The flexor pollicis longus (FPL) tendon ismost at risk.To assess the risk of flexor tendon injury, we evaluatedwith ultrasonography in 17 cadaveric hands(12 males and 5 females; mean age 77.1 years withrange of 45–94 years) the distance between the FPLand the most volar prominence. If direct frictionbetween the FPL and the prominence occured, possiblebulging of the FPL tendon over the prominencewas also measured. This assessment was performedwith and without the pronator quadratus (PQ) musclesectioned. This was repeated with a volar plate (volarplate 2.4 double column plate; Synthes) fixed proximalto the watershed line, with a volar plate fixed distalto the watershed line, and an LCP volar rim distal radius plate (Synthes) and a low-profile volar hookplate contouring the volar rim. Statistic analysis wasperformed with paired t test (p < 0.05).Mean distance from the FPL to the volar prominence(volar rim) decreased statistically significantly whenPQ was sectioned (0.3 mm) versus an intact PQ (1.5mm). Besides, mean distance also decreased statisticallysignificantly when a volar plate was fixed,even proximal to the watershed line with an intactPQ (0.4 mm) compared to no plate placed. Mean distancedecreased statistically significantly when thevolar plate was placed distal to the watershed line(−0.2 mm) versus proximal to the watershed line.Frequently (53%) bulging of the FPL over the prominenceof the plate occurred when volar plate wasplaced distal to the watershed line. When volar platewas placed proximal to the watershed line, mean distancealso decreased statistically significantly whenthe PQ was sectioned (0.1 mm) vs an intact PQ. Identicalresult was obtained when volar plate was placeddistal to the watershed line, since mean distance alsostatistically significantly decreased when the PQ wassectioned (−0.5 mm) versus an intact PQ. FPL bulgingincidence increased to 76%. Finally, mean distancedid not differ statistically significantly (p > 0.05) whenvolar rim plate was fixed contouring the volar rim(−0.1 mm range 0) versus a plate distal to the watershedline, although statistically significant increasewas measured when volar rim plate was placed withPQ repaired versus sectioned (−0.4 mm).Ultrasonography is a possible technique to evaluatepossible friction between the flexor tendons andthe volar plate prominence. Our results suggest theimportance of correct positioning of the volar plateproximal to the watershed line and the repairing of thepronator quadratus to increase the distance from theflexor pollicis longus tendon to the volar prominence.Direct friction or bulging of the flexor tendons occurfrequently when plates are placed distal to the watershedline. Clinical studying with ultrasonography isnecessary to correspond these flexor tendon frictionor bulging reported on ultrasonography with clinicalsymptoms of flexor tendinopathy and to view the sustainabilityof pronator quadratus repair over time.

The lifetime risk of appendicitis is 6 to 7 % [1]. When appendicitis is clinically suspected, an appendicolith can be found in 30% of the patients [2]. An appendicolith may be retained post-operatively ('dropped appendicolith') due to previous perforation, non-recognition during surgery or the impossibility to remove it. Abscesses that result from ectopic appendicoliths tend to occur paraceacally in the vicinity of Morrison's pouch and should be removed to prevent abscess development and possible overt sepsis [3]. As far as we know, we describe the first documented case of an intrahepatic localization of a dropped appendicolith causing a liver abscess.

Purpose To determine the changes in temperature within the gravid miniature pig uterus during magnetic resonance (MR) imaging at 3 T. Materials and Methods The study received ethics committee approval for animal experimentation. Fiber-optic temperature sensors were inserted into the fetal brain, abdomen, bladder, and amniotic fluid of miniature pigs (second trimester, n = 2; third trimester, n = 2). In the first trimester (n = 2), the sensors were inserted only into the amniotic fluid (three sacs per miniature pig, for a total of six sacs). Imaging was performed with a 3-T MR imager by using different imaging protocols in a random order for animal, each lasting approximately 15 minutes. The first regimen consisted of common sequences used for human fetal MR examination, including normal specific absorption rate (SAR). The second regimen consisted of five low-SAR sequences, for which three gradient-echo sequences were interspersed with two diffusion-weighted imaging series. Finally, a high-SAR regimen maximized the radiofrequency energy deposition (constrained by the 2-W per kilogram of body weight SAR limitations) by using five single-shot turbo spin-echo sequences. Differences in temperature increases between the three regimens and between the three trimesters were evaluated by using one-way analysis of variance. The maximum cumulative temperature increase over 1 hour was also evaluated. Results Low-SAR regimens resulted in the lowest temperature increase (mean ± standard deviation, -0.03°C ± 0.20), normal regimens resulted in an intermediate increase (0.31°C ± 0.21), and high-SAR regimens resulted in the highest increase (0.56°C ± 0.20) (P < .0001). Mean temperature increase in the third trimester was 0.38°C ± 0.27, with no significant differences compared with the first (0.23°C ± 0.27) and second (0.25°C ± 0.32) trimesters (P = .07). The cumulative temperature increase over 1-hour imaging time with high SAR can reach 2.5°C. Conclusion In pregnant miniature pigs, the use of 3-T magnets for diagnostic MR imaging with normal SAR regimens does not lead to temperature increases above 1°C if imaging time is kept below 30 minutes. Longer imaging time, especially with high-SAR regimens, can lead to an increase of 2.5°C. (©) RSNA, 2015 Online supplemental material is available for this article.

During nuclear medicine procedures technologists are exposed to relatively high extremity doses as a result of manipulation of syringes and vials. These manipulations also involve a risk on contamination with liquids that have a relatively high specific activity. Despite the fact that contaminations should be avoided by hygienic measures, they can occur by accidental spills or as a result of cross-contamination. It should be stated that even minor contaminations can lead to major extremity doses especially in the case of beta-emitters. This means that contamination survey followed by decontamination, where appropriate, is needed in routine practise. Regular survey by workers asks for self-discipline, is time-consuming and consequently often neglected. Moreover, the use of common contamination monitors does not reveal reliable quantitative data that can be used in calculation of cumulated doses. In this study contaminations were monitored during a long-term survey with a protocol based on fast identification, localisation and quantification. During the first 5 months of the survey 300 inspections were carried out among 10 technologists. Contamination was found in 28 (9%) cases (23 (99m)Tc-labelled radiopharmaceuticals, 5 (18)FDG). All detected contaminations were highly localised with values ranging from 185Bq to 440 kBq. The skin dose rates were calculated using different reference data and methods. The follow-up of individual contaminations resulted in the calculation of effective half-lives that are strongly radiopharmaceutical related. The use of these effective half-lives, the estimated exposure time and the reference data for dose rates resulted in a wide range of cumulated skin doses ranging from 8 mu Sv to 33 mSv. The first results of this survey indicate that extremity doses resulting from contaminations can have a large contribution to the total extremity dose of nuclear medicine technologists. (C). 2011 Elsevier Ltd. All rights reserved.

Significant staff exposure is generally expected during PET-and PET/CT applications. Whole-body doses as well as extremity doses are usually higher per procedure compared with SPECT applications. Dispensing individual patient doses and manual injection involves high extremity doses even when heavy weighted syringe shields are used. In some cases the external radiation causes an exposure to the fingertips of more than 500 mSv y(-1), which is the yearly limit. Whole-body doses per procedure are relatively lower compared with extremity doses and are generally spread over the entire procedure (Guillet, B., Quentin, P., Waultier, S., Bourrelly, M., Pisano, P. and Mundler, O. Technologist radiation exposure in routine clinical practice with 18F-FDG PET. J. Nucl. Med. Technol. 33, 175-179 (2005). Optimisation of the individual workload is often used to restrict staff doses, but many PET centres face the need for further optimisation to reduce the staff doses to an acceptable level. During this study the effect of the use of an automated dispensing and injection system for (18)FDG on whole-body doses and extremity doses was evaluated. Detailed dosimetric studies using thermoluminescent and direct ion storage dosimetry were carried out before and after the introduction of this system. The results show that the extremity doses can be reduced by more than 95 % up to a mean level of 10 muSv per handled GBq. At the same time, whole-body doses can be halved during injection of the tracer. This results in a dose reduction of 20 % during the entire procedure of injection, escorting and positioning. In this way, the study shows that with the use of automated dispensing and injection a considerable staff dose reduction can be obtained.

OBJECTIVE: The purpose of this study was to compare the time-course of contrast-enhancement in spleen and liver using Exia 160 in comparison with Fenestra LC and VC in healthy mice. PROCEDURES: Healthy C57bl/6 mice were used in this study. Fenestra LC and VC was administered intravenously at a dose of 0.1 ml/20 g or 0.2 ml/20 g. Exia 160 at a dose of 0.05 ml/20 g or 0.1 ml/20 g. Each animal underwent a micro-CT scan before contrast injection (baseline) and immediately after contrast injection. Additional scans were performed at 1, 2, 3, 4, 24, and 48 h after contrast administration. The mice who received Exia 160 were also scanned after 15, 30, and 45 min. RESULTS: The peak enhancement of Exia 160 occurred after 15 min for the spleen and after 30 min for the liver. CONCLUSIONS: Exia 160 allows rapid spleen and liver enhancement. The high iodine content results in small injection volumes.

There is a need to generate the next-generation vectors for gene therapy of muscle disorders in order to express higher levels of the therapeutic transgene at lower vector doses. This should minimize the risk of immune responses and toxic effects. Moreover, the availability of more potent vectors would also ease manufacturing constraints. To increase the potency of gene therapy for muscle disorders, such as Duchenne muscular dystrophy (DMD), we explored the use of novel genome-wide computational strategies to boost vector performance. This resulted in the identification of hyperactive transcriptional cisregulatory modules (i.e. CRMs) associated with a robust 200 to 400-fold increase in skeletal muscle-specific gene expression following AAV9-mediated transduction in mice. We then confirmed by chromatin immunoprecipitation that the CRMs contained clusters of muscle-specific transcription factor binding sites that accounted for high muscle-specific expression. We further validated the performanceof these muscle-specific CRMs to boost expression of micro-dystrophin and follistatin, as an effective combination gene therapy, in mdx/SCID mice. Subsequently, we injected AAV9 vectors that expressed microdystrophin (micro-DYS) and follistatin (FST) from the de novo designed CRMs into dystrophic mdx/SCID mice. This resulted in stable and widespread expression of the therapeutic micro- DYS and FST proteins in skeletal muscle and heart, as confirmed by immunohistochemistry and ELISA, respectively. Most importantly, the high expression levels of micro-DYS and FST led to a robust functional correction of the dystrophic phenotype of the treated mdx/SCID mice by assessing physical fitness and endurance using a treadmill assay. This opens new perspectives for muscle-directed gene therapy.

Introduction: The purpose of this study was to investigate the effect of nicotine patches (NP) on cognitive processes linked to cigarette addiction and craving. Materials and Methods: An fMRI experiment (3T, Achieva, Philips) was performed on five healthy volunteers (age 18–26 years; 1 male, 4 females) with smoking addiction (FTND C 4) in four random conditions and 1-week interscan interval: regular smoking (S); smoking deprivation for 14 h (SD) prior to the scan; smoking deprivation for 14 h combined with a 21 mg nicotine patch (SD + NP); and smoking deprivation for 14 h combined with a 0 mg placebo patch (SD + PP). Visual stimulation was provoked in block design by randomly displaying 42 images of smoking related scenes alternating with neutral images. First and second level analysis was performed for image processing. ANOVA was used to compare average group activations between conditions. Results were also compared to a non-smoking control group (N = 5). The standard Questionnaire for Smoking Urges (QSU) on a 7-point scale was simultaneously obtained immediately before and after each scan. Non-smokers were compared to smokers in all conditions. Cases: The QSU showed that craving significantly increased from 1.63 ± 1.01 in the S condition to 3.34 ± 1.94 after performing the experimental fMRI scan. Between conditions, only significant differences were seen when comparing SD (5.59 ± 1.33) with S (1.63 ± 1.01) or SD + NP (2.52 ± 1.23). The fMRI imaging results showed frontal and limbic activation in non-smokers when comparing to all conditions in smokers. During the S condition, significant activation was seen in the limbic system, attention areas and frontal regions compared to SD + NP, SD + PP and SD. In the SD + NP condition, limbic circuit and attention area were activated compared to SD and SD + PP. The SD + PP and SD condition showed activation in different areas of the frontal cortex and limbic system compared to S, SD + NP conditions. Discussion: The QSU showed a significant difference between SD condition and when nicotine is present (S and SD + NP), and thus nicotine reduced craving. The fMRI experiment revealed lower activity in areas associated with attention when nicotine lacks (SD + PP and SD). In line with the QSU results, areas involved with craving showed less activity when nicotine is present (S and SD + NP). References: Menossi HS, Goudriaan AE, Azevedo-Marques Pe´rico C, de Andrade AG, D’Elia G, Li CS, Castaldelli-Maia JM. (2013) Neural bases of pharmacological treatment of nicotine dependence—insights from functional brain imaging: a systematic review. CNS Drugs; 27(11): 921–941.

Objectives The present study was performed to determine normal values for gastric half-emptying time (t1/2GE) of liquids in healthy children. Methods Gastric emptying (GE) of a standardized test milk-drink measured with technetium scintigraphy and the C-acetate breath test (C-ABT) was compared in 19 children ages between 4 and 15 years with upper gastrointestinal symptoms. The C-ABT was subsequently used to determine normal values for GE of the same liquid test meal in 133 healthy children ages between 1 and 17 years. Results In the group of children with upper gastrointestinal symptoms, the results showed a significant correlation (r = 0.604, P = 0.0006) between t1/2GE measured with both techniques. In the group of healthy children, the results of t1/2GE showed that there was no influence of age, sex, weight, height, and body mass index on GE. Conclusions Normal values for GE of a standardized test milk-drink in healthy children were determined with the C-ABT. This technique is considered reliable and is well accepted by the patients.

The anatomy of the nerves of the foot and ankle is complex, and familiarity with the normal anatomy and course of these nerves as well as common anatomic variants is essential for correct identification at imaging. Ultrasonography (US) and magnetic resonance (MR) imaging allow visualization of these nerves and may facilitate diagnosis of various compression syndromes, such as "jogger's heel," Baxter neuropathy, and Morton neuroma. It may be difficult to distinguish the nerves from adjacent vasculature at MR imaging, and US can help in differentiation. The authors review the normal anatomy and common variants of the nerves of the foot and ankle, with use of dissected specimens and correlative US and MR imaging findings. In addition, the authors illustrate proper probe positioning, which is essential for visualizing the nerves at US. The authors' discussion focuses on the superficial and deep peroneal, sural, saphenous, tibial, medial and lateral plantar, medial and inferior calcaneal, common digital, and medial proper plantar digital nerves.

We report the CT findings in a case of partial anomalous pulmonary venous return (PAPVR) from the left upper lobe in an adult. PAPVR is an anatomic variant in which one to three pulmonary veins drain into the right atrium or its tributaries, rather than into the left atrium. This results in a left-to-right shunt with varying clinical presentation. These can range from asymptomatic patients to advanced cardiac failure.

An asymptomatic obese 60-year-old man with an increased cardiovascular risk profile (arterial hypertension and hypercholesterolemia) was checked prior to hip surgery. Resting ECG was normal. Exercise test was not possible. A dipyridamole myocardial perfusion scintigraphy showed inferolateral ischemia and a preserved left ventricular (LV) function. Coronary angiography demonstrated moderate atherosclerosis in the proximal segment of the right coronary artery (RCA) and a moderate stenosis in the distal segment of the posterolateral branch (Fig. A). The left anterior descending artery (LAD) and diagonal branches were visualized simultaneously. No additional coronary ostium could be found. The contrast enhanced cardiac CT was performed and it confirmed the absence of a left coronary ostium and a single RCA with two large right ventricular (RV) branches continuing to the left coronary artery (LCA). The first RV branch continued to the diagonal branch. The second RV branch continued to the LAD. Interestingly, in the anterior interventricular sulcus, the LAD had a bidirectional course proximally and distally, with proximally the emergence of an hypoplastic left circumflex artery (LCX) (Fig. B, C). None of the branches were running between the pulmonary artery and the ascending aorta, corresponding with a R-II A classification according to Lipton/ Yamanaka.

UNLABELLED: Human epidermal growth factor receptor 2 (HER2) status is one of the major tumor characteristics in breast cancer to guide therapy. Anti-HER2 treatment has clear survival advantages in HER2-positive breast carcinoma patients. Heterogeneity in HER2 expression between primary tumor and metastasis has repeatedly been described, resulting in the need to reassess HER2 status during the disease course. To avoid repeated biopsy with potential bias due to tumor heterogeneity, Nanobodies directed against HER2 have been developed as probes for molecular imaging. Nanobodies, which are derived from unique heavy-chain-only antibodies, are the smallest antigen-binding antibody fragments and have ideal characteristics for PET imaging. The primary aims were assessment of safety, biodistribution, and dosimetry. The secondary aim was to investigate tumor-targeting potential. METHODS: In total, 20 women with primary or metastatic breast carcinoma (score of 2+ or 3+ on HER2 immunohistochemical assessment) were included. Anti-HER2-Nanobody was labeled with (68)Ga via a NOTA derivative. Administered activities were 53-174 MBq (average, 107 MBq). PET/CT scans for dosimetry assessment were obtained at 10, 60, and 90 min after administration. Physical evaluation and blood analysis were performed for safety evaluation. Biodistribution was analyzed for 11 organs using MIM software; dosimetry was assessed using OLINDA/EXM. Tumor-targeting potential was assessed in primary and metastatic lesions. RESULTS: No adverse reactions occurred. A fast blood clearance was observed, with only 10% of injected activity remaining in the blood at 1 h after injection. Uptake was seen mainly in the kidneys, liver, and intestines. The effective dose was 0.043 mSv/MBq, resulting in an average of 4.6 mSv per patient. The critical organ was the urinary bladder wall, with a dose of 0.406 mGy/MBq. In patients with metastatic disease, tracer accumulation well above the background level was demonstrated in most identified sites of disease. Primary lesions were more variable in tracer accumulation. CONCLUSION: (68)Ga-HER2-Nanobody PET/CT is a safe procedure with a radiation dose comparable to other routinely used PET tracers. Its biodistribution is favorable, with the highest uptake in the kidneys, liver, and intestines but very low background levels in all other organs that typically house primary breast carcinoma or tumor metastasis. Tracer accumulation in HER2-positive metastases is high, compared with normal surrounding tissues, and warrants further assessment in a phase II trial.

Young plants of the viviparous Rhizophoraceae mangrove tree species start their development from fruit to seedling when still attached to the parent tree. These seedlings consist of an elongated cylinder-shaped hypocotyl (15-70 cm long, 0.5-3 cm diameter) (Tomlinson 1994). The hypocotyl plays a role as floating organ during hydrochorous dispersal once the seedlings abscise from the parent tree and stores nutrients used for fast rooting and settlement needed for survival in the harsh and highly dynamic mangrove environment (Youssef & Saenger 1996, Smith & Snedaker 2000). To better understand the ecological and biogeographical success of mangroves, more thorough knowledge is required on the development of the hydraulic system in mangrove saplings. We investigated the proportional changes in hypocotyl tissues over time in two Rhizophoraceae mangrove species (Bruguiera gymnorrhiza and Ceriops tagal) and the vessel network and characteristics in B. gymnorrhiza saplings, as a crucial step towards this understanding. We made use of X-ray Computed Tomography (CT) and high-resolution CT (μCT). CT allowed visualizing plant tissues in a non-destructive way as whole living plants could be scanned, hence their internal development over time could be followed. In contrast, μCT offered high resolution images of certain plant parts and therefore allowed investigating plant hydraulic characteristics in more and better detail than CT. Both techniques produced a continuous series of two-dimensional density images through an object (Brodersen et al. 2011), and combined with conventional destructive microsectioning procedures they provided us with a more complete picture of the internal development of young mangrove plants.

UNLABELLED: Tumor-associated macrophages constitute a major component of the stroma of solid tumors, encompassing distinct subpopulations with different characteristics and functions. We aimed to identify M2-oriented tumor-supporting macrophages within the tumor microenvironment as indicators of cancer progression and prognosis, using PET imaging. This can be realized by designing (18)F-labeled camelid single-domain antibody fragments (sdAbs) specifically targeting the macrophage mannose receptor (MMR), which has been identified as an important biomarker on this cell population. METHODS: Cross-reactive anti-MMR sdAbs were generated after immunization of an alpaca with the extracellular domains of both human and mouse MMR. The lead binder was chosen on the basis of comparisons of binding affinity and in vivo pharmacokinetics. The PET tracer (18)F-fluorobenzoate (FB)-anti-MMR sdAb was developed using the prosthetic group N-succinimidyl-4-(18)F-fluorobenzoate ((18)F-SFB), and its biodistribution, tumor-targeting potential, and specificity in terms of macrophage and MMR targeting were evaluated in mouse tumor models. RESULTS: Four sdAbs were selected after affinity screening, but only 2 were found to be cross-reactive for human and mouse MMR. The lead anti-MMR 3.49 sdAb, bearing an affinity of 12 and 1.8 nM for mouse and human MMR, respectively, was chosen for its favorable in vivo biodistribution profile and tumor-targeting capacity. (18)F-FB-anti-MMR 3.49 sdAb was synthesized with a 5%-10% radiochemical yield using an automated and optimized protocol. In vivo biodistribution analyses showed fast clearance via the kidneys and retention in MMR-expressing organs and tumor. The kidney retention of the fluorinated sdAb was 20-fold lower than a (99m)Tc-labeled counterpart. Compared with MMR- and C-C chemokine receptor 2-deficient mice, significantly higher uptake was observed in tumors grown in wild-type mice, demonstrating the specificity of the (18)F tracer for MMR and macrophages, respectively. CONCLUSION: Anti-MMR3.49 was denoted as the lead cross-reactive MMR-targeting sdAb. (18)F radiosynthesis was optimized, providing an optimal probe for PET imaging of the tumor-promoting macrophage subpopulation in the tumor stroma.

Background The natural evolution of treated symptomatic pulmonary embolism shows often incomplete resolution of pulmonary thrombi. The prevalence of perfusion defects depend on the image modality used. This study directly compares V/Q SPECT with DECT. Methods A single-center prospective observational cohort study of patients with intermediate risk PE, reassessed at the end of treatment with V/Q SPECT. Abnormal V/Q SPECT images were compared with DECT. Results We compared DECT en V/Q SPECT in 28 consecutive patients with persistent V/Q mismatch on V/Q SPECT, 13 men and 15 woman, mean age 60 ( + 17), range 23–82 year. One patient was excluded from the final analysis due to inferior quality DECT. In 18/27 (66.7%) the results were concordant between CTPA (persistent embolus visible), DECT (segmentary defects on iodine map) and V/Q SPECT (segmentary ventilation–perfusion mismatch). In 3/18 (11.1% of the total group) the partialy matched V/Q SPECT defect could be explained on DECT lung images by lung infarction. In 6/27 (22.1%) only hypoperfusion was seen on DECT iodine map. In 3/27 (11.1%) results were discordant between V/Q SPECT and DECT images. Conclusion Six months after diagnosis of first or recurrent PE, residual pulmonary perfusion-defects encountered on V/Q-SPECT corresponds in the majority of patients with chronic thromboembolic disease seen on DECT. In 22.1% of patients V/Q SPECT mismatch only corresponds with hypoperfusion on iodine map DECT scan. Some (11.1%) of the chronic thromboembolic lesions seen on V/Q SPECT can not be explained by DECT results.

Background The application of accelerated high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) could be a potential treatment option for alcohol-dependent patients and may result in a faster clinical response. In this open-label HF-rTMS feasibility study, we wanted to replicate previous findings of baseline brain activation as a predictor of relapse, and to evaluate how this intervention influences the relapse neurocircuit of “treatment-seeking” alcohol-dependent patients, by means of functional magnetic resonance imaging (fMRI) cue-exposure paradigms. Because relapsing patients have a diminished resilience of the emotion regulation/cognitive control system, before HF-rTMS treatment, we expected lower neuronal activation of especially the ventromedial prefrontal cortex and anterior cingulate cortex (ACC) during the presentation of alcohol-related cues in these patients. The relapse neurocircuit should be modified after accelerated HF-rTMS treatment, only in those patients who did not relapse. Methods After being administered a single sham-controlled HF-rTMS session (20 Hz to 110% motor threshold), 19 alcohol-dependent patients received an accelerated HF-rTMS protocol, consisting of 14 right dorsolateral prefrontal cortical sessions spread over 3 days. Before and after stimulation, during fMRI patients were confronted with a block and an event-related alcoholic cue-exposure paradigm. Relapse was defined as the consumption of any amount of alcohol within 4 weeks after the stimulation. A region of interest analysis was performed to evaluate how HF-rTMS exerts its effect. Results After 4 weeks, 13 of 19 patients had already consumed alcohol. When abstainers were compared to patients who had relapsed, we found higher dorsal ACC (dACC) activation at baseline, but only during the blocked cue-exposure paradigm. The effects of HF-rTMS on dACC blood oxygen level-dependent response were negatively correlated with the baseline dACC activation. Due to susceptibility artifacts located at the ventral cortical aspects in 6 of our participants, reliable data were only obtained for the ACC. Conclusions Our data indicate that higher baseline dACC activation may serve as a protective mechanism regarding relapse. For the first time, it is demonstrated that accelerated HF-rTMS treatment influences dACC activation in a rate-dependent manner: the lower the baseline dACC activation, the more dACC activity was increased after HF-rTMS treatment.

Background: The purpose of this in vivo study was to compare axillary artery blood flow velocity, and maximal handgrip strength and endurance performance in young subjects with and without an axillary arch (AA). Materials and methods: One hundred and fifty-six young adults were screened for the presence of an AA on their dominant arm side. After physical examination subjects were checked using diagnostic echography for the presence of an AA. Sixteen subjects with an AA and 15 without an AA had their axillary artery peak systolic velocity quantified in 3 different arm positions using Doppler ultrasound. Maximal handgrip strength and endurance performance was quantified in the same positions using a functional rehabilitation system. Results: Mean peak systolic velocity was significantly higher in the AA group compared to controls in abduction/external rotation of the arm during muscle relaxation (p = 0.003) and contraction (p = 0.01). No significant differences between groups were found for maximal handgrip strength and endurance performance. Conclusions: This study provides evidence for a transient axillary artery compression by the AA in a throwing position. This is not reinforced by additional contraction of the shoulder muscles along with the AA. Axillary artery compression does not influence maximal handgrip strength and endurance performance in symptom-free young adults.

The scapholunate joint is one of the most involved in wrist injuries. Its stability depends on primary and secondary stabilisers forming together the scapholunate complex. This ligamentous complex is often evaluated by wrist arthroscopy. To avoid surgery as diagnostic procedure, optimization of MR imaging parameters as use of three-dimensional (3D) sequences with very thin slices and high spatial resolution, is needed to detect lesions of the intrinsic and extrinsic ligaments of the scapholunate complex. The paper reviews the literature on imaging of radial-sided carpal ligaments with advanced computed tomographic arthrography (CTA) and magnetic resonance arthrography (MRA) to evaluate the scapholunate complex. Anatomy and pathology of the ligamentous complex are described and illustrated with CTA, MRA and corresponding arthroscopy. Sprains, mid-substance tears, avulsions and fibrous infiltrations of carpal ligaments could be identified on CTA and MRA images using 3D fat-saturated PD and 3D DESS (dual echo with steady-state precession) sequences with 0.5-mm-thick slices. Imaging signs of scapholunate complex pathology include: discontinuity, nonvisualization, changes in signal intensity, contrast extravasation (MRA), contour irregularity and waviness and periligamentous infiltration by edema, granulation tissue or fibrosis. Based on this preliminary experience, we believe that 3 T MRA using 3D sequences with 0.5-mm-thick slices and multiplanar reconstructions is capable to evaluate the scapholunate complex and could help to reduce the number of diagnostic arthroscopies.

Learning objectives Background Findings and procedure details Conclusion Personal information References, Learning objectives: To understand the technical differences between digital tomosynthesis, fan beam CT and cone beam CT image acquisition To understand the challenges of imaging osteosynthesis material in 3D at high spatial resolution To illustrate the value of...

This paper presents a novel classification approach for microcalcifications extracted from core biopsy tissue samples digitized using micro-CT, a high-resolution 3D imaging modality. Microcalcifications are tiny spots of calcium that may occur in the female breast. Although they are common in healthy woman, they are often an early sign of breast cancer. In case of suspiciousness, a biopsy is conducted and the extracted tissue is pathologically analyzed for the presence of cancer cells. The calcifications themselves however are mostly not analyzed. As a result, there is a ground truth for the tissue samples but not for the individual calcifications. Therefore, this paper presents an approach where the calcifications are first classified according to shape-based clusters before predicting a label for the tissue samples.

In alcohol-dependent patients craving is a difficult-to-treat phenomenon. It has been suggested that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may have beneficial effects. However, exactly how this application exerts its effect on the underlying craving neurocircuit is currently unclear. In an effort to induce alcohol craving and to maximize detection of HF-rTMS effects to cue-induced alcohol craving, patients were exposed to a block and event-related alcohol cue-reactivity paradigm while being scanned with fMRI. Hence, we assessed the effect of right dorsolateral prefrontal cortex (DLPFC) stimulation on cue-induced and general alcohol craving, and the related craving neurocircuit. Twenty-six recently detoxified alcohol-dependent patients were included. First, we evaluated the impact of one sham-controlled stimulation session. Second, we examined the effect of accelerated right DLPFC HF-rTMS treatment: here patients received 15 sessions in an open label accelerated design, spread over 4 consecutive days. General craving significantly decreased after 15 active HF-rTMS sessions. However, cue-induced alcohol craving was not altered. Our brain imaging results did not show that the cue-exposure affected the underlying craving neurocircuit after both one and fifteen active HF-rTMS sessions. Yet, brain activation changes after one and 15 HF-rTMS sessions, respectively, were observed in regions associated with the extended reward system and the default mode network, but only during the presentation of the event-related paradigm. Our findings indicate that accelerated HF-rTMS applied to the right DLPFC does not manifestly affect the craving neurocircuit during an alcohol-related cue-exposure, but instead it may influence the attentional network.

Background and Purpose. To evaluate the added value of MRI with respect to peripheral quantitative computed tomography (pQCT) and dual energy X-ray absorptiometry (DXA) for predicting femoral strength.Material and Methods. Bone mineral density (BMD) of eighteen femur specimens was assessed with pQCT, DXA, and MRI (using ultrashort echo times (UTE) and the MicroView software). Subsequently biomechanical testing was performed to assess failure load. Simple and multiple linear regression were used with failure load as the dependent variable.Results. Simple linear regression allowed a prediction of failure load with either pQCT, DXA, or MRI in anr2range of 0.41–0.48. Multiple linear regression with pQCT, DXA, and MRI yielded the best prediction (r2=0.68).Conclusions. The accuracy of MRI, using UTE and MicroView software, to predict femoral strength compares well with that of pQCT or DXA. Furthermore, the inclusion of MRI in a multiple-regression model yields the best prediction.

We present a method for automatically estimating prosthesis migration from previous and follow-up CT image data. The method consists of the segmentation of the bone and prosthesis in both images, followed by a registration of both substructures. The migration is found by computing the difference between both transforms. In this work we assess the accuracy of the method for zero migration. The method was applied on data from a mechanical phantom and on patient data, both with zero migration. Our experiments show that an accuracy of less than 0.3 mm can be achieved in a clinical setting.

PURPOSE A dual-energy (DE) phantom study was performed on two scanner types in order to evaluate (1) the stability and accuracy of CT numbers and iodine concentrations in function of object size; (2) the effect of beam hardening. METHOD AND MATERIALS Iodine concentrations of 3 and 6 mgI/ml were poured into two respective rows of cylindrical cavities with diameters ranging from 3 to 25.5 mm in an AAPM CT performance phantom. Besides this, a 16 mm diameter tube filled with 6 mgI/ml was placed in the main water-filled compartment, partly covered by a Teflon beam hardening ring. The phantom was scanned in standard 120 kVp and DE mode on a GE Healthcare Discovery HD750 and Siemens SOMATOM Definition Flash scanner at 3 CTDIvol's (9, 19 and 29 mGy). Iodine concentrations were determined for all cavities using the scanner's DE mode, and compared to their true concentrations. CT number stability was determined accordingly and a comparison was made between the DE acquisition and standard 120 kV scanning. RESULTS (1) Relatively constant (max VAR 14%) HU values for both scanners as a function of the object diameters were observed. The Siemens scanner showed a consistent overestimate of approximately 0.5 mgI/ml for both contrast concentrations. A significant decrease in concentration accuracy for object diameters smaller than 6 mm was present for both scanners. (2) A step-like increase of 10 HU upon transitioning out of the Teflon part was observed for both scanners at single energy 120 kV and the Siemens blended DE image, less for the GE DE image (AV 148 HU, max VAR 5 HU). CONCLUSION (1) Measured and true iodine concentrations were consistent down to 6 mm object size, notwithstanding an observed offset with one scanner type. (2) A step-like increase in HU highlights the effect of beam hardening, and is more prominent for classical scans compared to DE. CLINICAL RELEVANCE/APPLICATION DE CT techniques are being increasingly used in tumor imaging. Since iodine is a contrast agent commonly used in CT imaging, determining its detectable lower limit is a crucial factor. Iodine concentration estimations should be made with appropriate consideration.

In dose comparison studies it is crucial that CTDI values are based on the same standard. Manufacturers should clearly communicate the applied CTDI method, and strive to implement the most recent standard. Although promising, the IEC3.1 method has not yet proven to be applicable for systems with larger minimal collimations and it also needs an approach to regularize the underestimated CTDI towards CTDI_full. Background The introduction of beam widths >4cm in CT deteriorates the paradigm of the standard CTDI_100 measurements with a 10cm pencil ionization chamber. Extension of the former CTDI definition for large beam widths is unpractical as it requires much larger phantoms. Several solutions have been published and two new standards have been recommended (IEC3.0 2009, IEC3.1 2010). Evaluation We assess the accuracy and differences between wide beam dosimetry methods for a 256-slice system (Revolution CT, GE Healthcare) and compare to the indicated values of the scanner. Weighted CTDI measurements were acquired in a body phantom for all available combinations of collimation (NxT=5-40-80-120-140-160 mm) and kVp (70-80-100-120-140): CTDI_full (='true' CTDI): CTDI obtained by 30 cm dose integration in two CTDI phantoms with 35cm length. IEC3.0: adapts the standard CTDI_100 definition for NxT>10cm by replacing the denominator NxT with the actual chamber length (10cm). IEC3.1: determines the CTDI for any NxT by multiplying the CTDI_100 of a reference collimation with the quotient of free-in-air CTDI measurements of NxT and reference collimation. All methods yield lower values than CTDI_full; the IEC 3.1 method provides a more constant deviation from CTDI_full than the IEC3.0 method. Deviations up to 23% for large beam widths are found between IEC methods. The indicated values of the scanner appear to follow the IEC 3.0 standard. Discussion The recent IEC3.1 method is a promising replacer for CTDI_full measurements. As manufacturers have not yet adopted IEC3.1, and also national legislations may not yet have implementedany wide beam CTDI standard, a uniformly used CTDI standard is not yet in sight, potentially resulting in large deviations (up to 25% and more) depending on the CTDI method used.

The truncated Hilbert transform with overlap $H_T$ is an operator that arises in tomographic reconstruction from limited data, more precisely in the method of Differentiated Back-Projection (DBP). Recent work [1] has shown that the singular values of this operator accumulate at both zero and one. To better understand the properties of the operator and, in particular, the ill-posedness of the inverse problem associated with it, it is of interest to know the rates at which the singular values approach zero and one. In this paper, we exploit the property that $H_T$ commutes with a second-order differential operator $L_S$ and the global asymptotic behavior of its eigenfunctions to find the asymptotics of the singular values and singular functions of $H_T$., Comment: 25 pages

Introduction: Nanobodies, the recombinantly produced antigen-binding domains of camelid heavy-chain antibodies, have already proven to be proficient probes for non-invasive nuclear imaging (1). To safeguard their intrinsically high binding specificity and affinity and to ensure the tracer’s homogeneity, methods to site-specifically label them have been developed (2,3). We investigated the use of Sortase A, a transpeptidase enzyme derived from Staphylococcus aureus that catalyzes the conjugation between an LPXTG-tagged protein and an oligoglycine-functionalized probe (4). Methods: The sortase-recognition sequence LPETG (sortag) was introduced at the C-terminal end of the Nanobody, upstream of the hexahistidine-tag. As a proof-of-concept the chelating agent CHX-A’’-DTPA was functionalized with an N-terminal triglycine. After the enzymatic conjugation a straightforward IMAC and SEC purification strategy was applied. The purified compound was analyzed using ESI-Q-TOF mass spectrometry. After radiolabeling with indium-111, the new Nanobody-based SPECT imaging probe was validated in a HER2-expressing tumor model. Results: The clinical lead compound Nanobody 2Rs15d was generated with a sortag and conjugated to the triglycine-functionalized chelating agent CHX-A’’-DTPA with the use of Sortase. After IMAC and SEC purification, a yield of 30-50% single-conjugated product was obtained and confirmed by mass spectrometry analysis. Radiolabeling with indium-111 resulted in a high radiochemical purity (≥ 98%). After in vitro validation (surface plasmon resonance, cell binding study, stability in serum) the new tracer construct was validated in vivo. Nanobody 111In-CHX-A’’-DTPA-2Rs15d-sortag was able to target the HER2-positive tumor specifically (5.03 ± 3.36 %IA/g vs. 0.35 ± 0.25 %IA/g for a non-targeting control Nanobody) in BT474M1-xenografted mice and visualize the tumor with high contrast at 4 h p.i. Conclusions: These results provide a versatile and standardized strategy for the site-specific labeling of Nanobodies. Using the sortase-mediated conjugation strategy any oligoglycine-functionalized label or chelating agent could be attached to the targeting probe, resulting in a homogeneous population of tracers for use in molecular imaging. References: (1) De Vos et al. (2013) Expert Opin. Biol. Ther. 13, 1149-1160. (2) Xavier et al. (2012) Methods Mol. Biol. 911, 485-490. (3) Massa et al. (2014) Bioconjug. Chem. 25, 979-988. (4) Popp et al. (2007) Nature Chem. Biol. 3, 707-708. Key Words: Site-specific labeling, Homogeneous, Nanobody

The location and extent of white matter lesions on magnetic resonance imaging (MRI) are important criteria for diagnosis, follow-up and prognosis of multiple sclerosis (MS). Clinical trials have shown that quantitative values, such as lesion volumes, are meaningful in MS prognosis. Manual lesion delineation for the segmentation of lesions is, however, time-consuming and suffers from observer variability. In this paper, we propose MSmetrix, an accurate and reliable automatic method for lesion segmentation based on MRI, independent of scanner or acquisition protocol and without requiring any training data. In MSmetrix, 3D T1-weighted and FLAIR MR images are used in a probabilistic model to detect white matter (WM) lesions as an outlier to normal brain while segmenting the brain tissue into grey matter, WM and cerebrospinal fluid. The actual lesion segmentation is performed based on prior knowledge about the location (within WM) and the appearance (hyperintense on FLAIR) of lesions. The accuracy of MSmetrix is evaluated by comparing its output with expert reference segmentations of 20 MRI datasets of MS patients. Spatial overlap (Dice) between the MSmetrix and the expert lesion segmentation is 0.67 ± 0.11. The intraclass correlation coefficient (ICC) equals 0.8 indicating a good volumetric agreement between the MSmetrix and expert labelling. The reproducibility of MSmetrix' lesion volumes is evaluated based on 10 MS patients, scanned twice with a short interval on three different scanners. The agreement between the first and the second scan on each scanner is evaluated through the spatial overlap and absolute lesion volume difference between them. The spatial overlap was 0.69 ± 0.14 and absolute total lesion volume difference between the two scans was 0.54 ± 0.58 ml. Finally, the accuracy and reproducibility of MSmetrix compare favourably with other publicly available MS lesion segmentation algorithms, applied on the same data using default parameter settings., Highlights • MSmetrix is a new automatic method for white matter lesion segmentation based on MRI. • MSmetrix performs unsupervised segmentation using 3D T1-weighted and FLAIR MR images. • MSmetrix is validated on two MS datasets and shows good accuracy and reproducibility. • MSmetrix compares favourably with other publicly available MS lesion segmentation algorithms.

PURPOSE To investigate the impact of the administered contrast media iodine dose on the radiation induced DNA double-strand breaks in peripheral blood lymphocytes after a diagnostic cardiac CTA in a porcine model. METHOD AND MATERIALS A Göttingen minipig (Ellegaard, Denmark) was scanned with a constant cardiac CTA protocol (100 kV, Auto mA, ECG gated, 0-300% phase, CTDIvol = 45 mGy) on a Revolution CT (GE Healthcare) with an inter-scan delay of one week. We asses a range of contrast media with different iodine concentrations (0-160-200-320 mg I/mL) while keeping the injection parameters constant (3 mL/s and 60 mL followed by a 12 mL saline flush). Before and 15 min after each CT scan, blood samples were collected and put on ice. The lymphocytes were isolated from these blood samples and immunofluoresce microscopy was performed to quantify the γH2AX foci representing the radiation induced DNA double strand breaks. At least 750 lymphocytes were analyzed for each condition. Statistical analysis was performed using an independent sample t-test. RESULTS We report preliminary results of the first experiments without contrast media (0 mg I/mL) and with 320 mg I/mL contrast media iodine concentration. The amount of DNA double strand breaks was significantly higher when contrast media was present (0.45 ± 0.19 foci/cell) compared to the identical scan protocol without contrast media (0.17 ± 0.15 foci/cell) (p-value < 0.001). CONCLUSION The presence of iodine contrast has an impact on the amount of radiation induced DNA double strand breaks. The iodine blood concentration results in a higher photoelectric effect which lead to an increase in the formation of secondary electrons responsible for the induction of DNA double strand breaks. CLINICAL RELEVANCE/APPLICATION Due to the iodine dose dependent side effect of contrast media, the administration should be continuously reassessed in function of the evolving CT technology.

Background Limited radiologic literature is available to calculate the change in CTDIvol by changing the NI as used on the equipment of General Electric (GE, Milwaukee, USA). The guideline from GE provide an increase in noise of 5% and a decrease in mA of 10% per dose step. However, the appropriate NI is not easy to find whenever a substantial change in CTDIvol is desired. Evaluation We scanned 12 cadavers (GE CT750HD Discovery, autokV, dose modulation, slice thickness 0.625 mm, filtered back projection) with decreasing dose till 10% of the initial CTDIvol by adjusting the NI. This resulted in 12 datasets for CT thorax (CTT) and CT abdomen (CTA). The NI (x-axis) and the predicted CTDIvol (y-axis) were described in a graph. The relation between the NI and the CTDIvol is proportional to x^(-2.014 ± 0.039) for CTT and x^(-2.004 ± 0.002) for CTA (R^ = 0.999 ± 0.001, for both). The predicted CTDIvol displayed on the console was compared to the obtained CTDIvol in the dose report in 20 patients (CTT and CTA) in clinical practice. For our equipment, the obtained CTDIvol seemed 0.99 ± 0.01 % of the estimated CTDIvol. Discussion Noise, and by extension the NI, is not the only important parameter in the judgment of image quality. For instance, obese and some older patients have increased intrinsic contrast due to the augmented fat content. A radiologist or dedicated technician might find it appropriate to allow more noise in these patients images. Indeed, they develop an attitude for the right dose for the right indication by experience. The inverse quadratic function provides us with the opportunity to calculate the NI belonging to a certain CTDIvol, from which we know by experience that it results in diagnostic image quality for that patient. CONCLUSION The guideline from GE (see background) is usefull for subtile adjustments of protocols. Whenever a more substantial change in CTDIvol is desired, the relation (CTDIvol/NI^²)_1 = (CTDIvol/NI^²)_2 is recommended to calculate the associated NI more quickly.

PURPOSE: To investigate a computed tomographic (CT) protocol with iterative reconstruction at conventional radiography dose levels for the assessment of structural lung abnormalities in patients with cystic fibrosis ( CF cystic fibrosis ). MATERIALS AND METHODS: In this institutional review board-approved study, 38 patients with CF cystic fibrosis (age range, 6-58 years; 21 patients 18 years) underwent investigative CT (at minimal exposure settings combined with iterative reconstruction) as a replacement of yearly follow-up posteroanterior chest radiography. Verbal informed consent was obtained from all patients or their parents. CT images were randomized and rated independently by two radiologists with use of the Bhalla scoring system. In addition, mosaic perfusion was evaluated. As reference, the previous available conventional chest CT scan was used. Differences in Bhalla scores were assessed with the χ(2) test and intraclass correlation coefficients ( ICC intraclass correlationcoefficient s). Radiation doses for CT and radiography were assessed for adults (>18 years) and children (

We developed, validated and assessed inter- and intraobserver reliability of a CT-scan based measurement tool to evaluate morphological characteristics of the bone–cement–stem complex of hip implants in cadaver femurs. Two different models were investigated: the stem-cavity model using a double tapered polished femoral-stem that is removed after cement curing and the plastic-replica model using a stereolithographic stem replica that is left in place during CT-scanning. Software was developed to segment and analyze connective CT-images and identify the contours of bone, cement, and stem based on their respective gray values. Volume parameters (whole specimen, cement, stem, air contents of bone and cement), concentricity parameters (distances between centroids of stem and cement, cement and bone, stem and bone), contact surfaces (bone/air and cement/bone) and bone cement mantle thickness parameters were calculated. A three-dimensional protocol was developed to evaluate the minimal mantle thickness out of the CT-plane. The average accuracy for surfaces within CT-images was 7.47 mm2 (1.80%), for bone and cement mantle thickness it was 0.51 mm (9.39%), for distances between centroids it was 0.38 mm (18.5%) and contours: 0.27 mm (2.57%). The intra- and interobserver reliability of air content in bone and cement was sub-optimal (intraclass-correlation coefficient (ICC) as low as 0.54 with an average ICC of 0.85). All other variables were reliable (ICC > 0.81, average ICC: 0.96). This in vitro technique can assess characteristics of cement mantles produced by different cementing techniques, stem types or centralizers.

We report our experience with computed tomography (CT) fluoroscopic-guided cutting needle biopsy of intrapulmonary lesions, which combines the advantage of real-time monitoring of the procedure with cross-sectional imaging of the target lesion. Sixty-six consecutive real-time CT fluoroscopy-guided biopsies of strictly intrapulmonary lesions were performed in 63 patients. A pneumothorax was detected in 19 of 66 patients (28.7%), only 1 of which however required drainage. Alveolar hemorrhage was seen in 14 of 66 patients (21%). There was no hemoptysis. Two patients had both a pneumothorax and an alveolar hemorrhage. We found no correlation between the occurrence of a pneumothorax and the age of the patient (P = 0.119) or the FEV1% pred (P = 0.55). There is a strong correlation between the occurrence of a pneumothorax and the length of the intrapulmonary trajectory (P < 0.001), the lesion diameter (P < 0.001), the needle thickness (P < 0.001), and the number of needle passes (P < 0.001). Diagnostic sensitivity for malignant lesions was 86%, specificity 100%, and accuracy 86%. Sensitivity for benign disease was 100% with a specificity of 40%. CT fluoroscopy-guided core needle biopsy offers good diagnostic sensitivity for both malignant and benign disease at a low complication rate even in small intrapulmonary lesions. Nonspecific benign histology should warrant caution and follow-up study.

Current methods for sentinel lymph node (SLN) mapping involve the use of radioactivity detection with technetium-99m sulfur colloid and/or visually guided identification using a blue dye. To overcome the kinetic variations of two individual imaging agents through the lymphatic system, we report herein on two multifunctional macromolecules, 5a and 6a, that contain a radionuclide ( 99m Tc or 68 Ga) and a near-infrared (NIR) reporter for pre- and/or intraoperative SLN mapping by nuclear and NIR optical imaging techniques. Both bimodal probes are dextran-based polymers (10 kDa) functionalized with pyrazole-diamine (Pz) or 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra- acetic acid (DOTA) chelating units for labeling with fac-( 99m Tc(CO)3) + or 68 Ga(III), respectively, mannose units for receptor targeting, and NIR fluorophore units for optical imaging. The probes allowed a clear visualization of the popliteal node by single-photon emission computed tomography (SPECT/CT) or positron emission tomography (PET/CT), as well as real-time optically guided excision. Biodistribution studies confirmed that both macromolecules present a significant accumulation in the popliteal node (5a: 3.87 ± 0.63% IA/organ; 6a: 1.04 ± 0.26% IA/ organ), with minimal spread to other organs. The multifunctional nanoplatforms display a popliteal extraction efficiency >90%, highlighting their potential to be further explored as dual imaging agents.

We present an analysis of weakly convex discontinuity adaptive (WCDA)models for regularizing three-dimensional (3D) quantitative microwave imaging. In particular, we are concerned with complex permittivity reconstructions from sparse measurements such that the reconstruction process is significantly accelerated. When dealing with such a highly underdetermined problem, it is crucial to employ regularization, relying in this case on prior knowledge about the structural properties of the underlying permittivity profile: we consider piecewise homogeneous objects. We present a numerical study on the choice of the potential function parameter for the Huber function and for two selected WCDA functions, one of which (the Leclerc-Cauchy-Lorentzian function) is designed to be more edge-preserving than the other (the Leclerc-Huber function). We evaluate the effect of reducing the number of (simulated) scattered field data on the reconstruction quality. Furthermore, reconstructions from subsampled single-frequency experimental data from the 3D Fresnel database illustrate the effectiveness of WCDA regularization.

BACKGROUND: To combine the sensitivity of bioluminescent imaging (BLI) with the 3D and quantitative properties of pinhole single-photon emission computed tomography (SPECT)/micro-computed tomography (CT) (phSPECT/micro-CT), we generated stable cell lines that express a yellow-fluorescent protein (YFP) and Gaussia luciferase (GLuc) fusion protein (YFP/GLuc). For in vivo phSPECT detection of this YFP/GLuc protein, a nanobody, targeted against yellow and green fluorescent proteins (anti-YFP-Nb), was site specifically labelled with (99m)Tc. METHODS: Human embryonic kidney cells (HEK293T) were cultured and passaged every 3 days. 10E5 cells were transduced with YFP/GLuc-containing vector: both membrane-targeted (MT-YFP/GLuc) and non-targeted (YFP/GLuc) fusion proteins were developed. These vectors were compared against a SKOV-3 cell line stably expressing green fluorescent-firefly luciferase (GFP/Fluc) and HEK293T cells expressing red fluorescent protein in combination with a Gaussia luciferase (Red/GLuc). Transduction efficiencies were scored by fluorescence microscopy, and transduced cells were enriched by fluorescence-activated cell sorting (FACS). GLuc and FLuc functionality was tested in vitro by list-mode BLI. Subsequently, cells were transplanted subcutaneously in athymic (nu/nu) mice (MT-YFP/GLuc: n?=?4, YFP/GLuc: n?=?6, GFP/FLuc: n?=?6, Red/GLuc: n?=?4). Labelling efficiency of anti-YFP-Nb was measured using instant thin layer chromatography. One week after transplantation, (99m)Tc-labelled anti-YFP-Nb was injected intravenously and pinhole (ph) SPECT/micro-CT was performed, followed by in vivo BLI. RESULTS: Cells showed high levels of fluorescence after transduction. The cells containing the MT-YFP/GLuc were positive on fluorescence microscopy, with the fluorescent signal confined to the cell membrane. After cell sorting, transduced cells were assayed by BLI and showed a significantly higher light output both in vitro and in vivo compared with non-transduced HEK293T cells. The anti-YFP-Nb labelling efficiency was 98%, and subsequent phSPECT/micro-CT demonstrated visible cell binding and significantly higher transplant-to-muscle ratio for both the MT-YFP/GLuc and YFP/GLuc transplanted cells, compared with the GFP/FLuc and Red/GLuc group. CONCLUSION: This study provides a proof of principle for a nanobody-based cell tracking method, using a YFP/GLuc fusion protein and anti-YFP-Nb in a model of subcutaneously transplanted transduced HEK293T cells.

Bioluminescence imaging Bioluminescence imaging is a research technique that uses light-producing enzymes from naturally occurring species or modified versions of these enzymes to follow biological processes inside cells or animals. The luciferase enzyme is often encoded in a reporter gene that is introduced into the cells or animals of interest. The amount of light that is detected by a light-sensitive camera represents changes in the chosen biological process. In vivo Literally ‘in the living.’ Here, in vivo is used to refer to experiment performed in living animals. In vitro Literally ‘in glass.’ When experiments are performed in a laboratory vessel rather than a living organism. Here, all experiments performed outside a living animal are referred to as in vitro, although some authors still regard intact cell assays as in vivo since it still concerns living cells.

Through its role in (routine) patient care, nuclear medicine has set the standard for molecular imaging: the sensitivity and specificity of the available (multimodality) nuclear imaging technologies (SPECT/CT, PET/CTand PET/MR) are superior to those of any other clinical imaging modality. Nevertheless, efforts are ongoing to apply ultrasound, magnetic resonance and/or optical imaging techniques to molecular imaging in the clinic. A careful look at the theoretical detection sensitivities of the individual modalities readily confirms that especially ultrasound, optical and radionuclide techniques currently have the potential to visualize (low) biomarker expression levels using imaging probes [1]. Having said this, there are also activities regarding the development of MR contrast agents. Since the value of ultrasound technologies remains confined to the vascular network and the sensitivity of MR is still relatively low, only optical imaging can, in theory, match the sensitivity performance of nuclear medicine techniques.

UNLABELLED: (99m)Tc-cAbVCAM1-5, a single-domain antibody fragment directed against mouse or human vascular cell adhesion molecule 1 (VCAM-1), recently has been proposed as a new imaging agent for the detection of inflamed atherosclerotic lesions. Indeed, in a mouse model of atherosclerosis, (99m)Tc-cAbVCAM1-5 specifically bound to VCAM-1-positive lesions, thereby allowing their identification on SPECT images. The purpose of the present study was to investigate (99m)Tc-cAbVCAM1-5 imaging sensitivity using a reference statin therapy. METHODS: Thirty apolipoprotein E-deficient mice were fed a western-type diet. First, the relationship between the level of VCAM-1 expression and (99m)Tc-cAbVCAM1-5 uptake was evaluated in 18 mice using immunohistochemistry and autoradiography. Second, longitudinal SPECT/CT imaging was performed on control (n = 9) or atorvastatin-treated mice (0.01% w/w, n = 9). RESULTS: (99m)Tc-cAbVCAM1-5 uptake in atherosclerotic lesions correlated with the level of VCAM-1 expression (P < 0.05).Atorvastatin exerted significant antiatherogenic effects, and (99m)Tc-cAbVCAM1-5 lesion uptake was significantly reduced in 35-wk-old atorvastatin-treated mice, as indicated by ex vivo γ-well counting and autoradiography (P < 0.05). SPECT imaging quantification based on contrast-enhanced CT was reproducible (interexperimenter intraclass correlation coefficient, 0.97; intraexperimenter intraclass correlation coefficient, 0.90), and yielded results that were highly correlated with tracer biodistribution (r = 0.83; P < 0.0001). Therefore, reduced (99m)Tc-cAbVCAM1-5 uptake in atorvastatin-treated mice was successfully monitored noninvasively by SPECT/CT imaging (0.87 ± 0.06 vs. 1.11 ± 0.09 percentage injected dose per cubic centimeter in control group, P < 0.05). CONCLUSION: (99m)Tc-cAbVCAM1-5 imaging allowed the specific, sensitive, and reproducible quantification of VCAM-1 expression in mouse atherosclerotic lesions. (99m)Tc-cAbVCAM1-5 therefore exhibits suitable characteristics for the evaluation of novel antiatherogenic agents.

Nanobodies are single-domain, antigen-binding fragments derived from the heavy chain-only antibodies naturally occuring in Camelidae. Here we studied the use of anti-idiotype Nanobodies as an imaging tool in Multiple Myeloma (MM) using the 5T2MM murine model. This model is highly analogous to the human disease and is characterised by tumour expansion in the bone marrow, production and secretion of monoclonal paraprotein and bone lesions. After dromedary immunisation with 5T2MM idiotype we were able to isolate anti-idiotype Nanobodies. Their high affinity and specificity as demonstrated by ELISA, afinity binding assay and FACS analysis. Based on these results we selected the best binder (R3B23) fir further in vivo analyssis. R3B23 was labeled with 99mTC-tricarbonyl (99mTc-R3B23) for in vivo tracing. Healthy C57Bl/KaLwRij mice or 5T2MM diseased mice were i.v. injected with 99mTc-R3B23. One our post injection the miced were sacrificed and the radioactivity present in deifferent organs and tissues was measured.In the naive mice we observed high kidney and bladder uptake, and very low uptake in the other organs and tissues, indicating fast renal clearance. In the diseased animals, increased radioactivity was detected in all examined organs including blood, liver, spleen and bone. Using 99mTc-R3B23 we monitored disease progression: we scanned the 5T2MM mice by pinhole SPECT and micro-CT scan at different time points starting at week 1 after inoculation with 5T2MM cells into naive mice. Image analysis showed an increased 99mTc-R3B23 uptake starting at week 7 after tumour inoculation. At this time point no circulating M-spile could be detected by capillary electrophoresis. 99mTc-R3B23 was able to monitor therapeutic response in 5T2MM mice. After three weeks treatment with velcade (two days per week) we saw a clear decrease in Nanobody uptake compared to the untreated group. Our study shows that anti-idiotype Nanobodies are a new, sensitive, sêcific and non-invasive imaging tool in MM and provides the rationale forfurther studies on their clinical application. In addition Nanobodies can be coupled tot toxic agnets to target the MM cells.

Chemistry 19(24), 7847 - 7855 (2013). doi:10.1002/chem.201204015, n‐Heptyl α‐D‐mannoside (HM) has previously been identified as a nanomolar FimH antagonist able to prevent Escherichia coli adhesion. We have designed mono‐ and heptavalent glycoconjugates in which HM is tethered to β‐cyclodextrin (β‐CD) through short and long spacers. One‐pot click or co‐clicking procedures were developed to directly obtain the glycoconjugates from unprotected HM and β‐CD precursors. These FimH antagonists were examined biophysically and in vivo. Reverse titrations by isothermal calorimetry led to trapping of the short‐tethered heptavalent β‐CD in a complex with three FimH lectins. Combined dynamic light scattering and small‐angle X‐ray solution scattering data allowed the construction of a model of the FimH trimer. The heptavalent β‐CDs were shown to capture and aggregate living bacteria in solution and are therefore also able to aggregate FimH when attached to different bacteria pili. The first in vivo evaluation of multivalent FimH inhibitors has been performed. The heptavalent β‐CDs proved to be much more effective anti‐adhesive agents than monovalent references with doses of around 2 μg instilled in the mouse bladder leading to a significantly decreased E. coli load. Intravenously injected radiolabeled glycoconjugates can rapidly reach the mouse bladder and >2 μg concentrations can easily be retained over 24 h to prevent fluxing bacteria from rebinding., Published by Wiley-VCH, Weinheim

Camelid-derived single-domain antibody-fragments (similar to 15 kDa), called nanobodies, are a new class of molecular tracers that are routinely identified with nanomolar affinity for their target and that are easily tailored for molecular imaging and drug delivery applications. We hypothesized that they are well-suited for the design of targeted microbubbles (mu Bs) and aimed to develop and characterize eGFP- and VCAM-1-targeted mu Bs. Anti-eGFP (cAbGFP4) and anti-VCAM-1 (cAbVCAM1-5) nanobodies were site-specifically biotinylated in bacteria. This metabolic biotinylation method yielded functional nanobodies with one biotin located at a distant site of the antigen-binding region of the molecule. The biotinylated nanobodies were coupled to biotinylated lipid mu Bs via streptavidin-biotin bridging. The ability of mu B-cAbGFP4 to recognize eGFP was tested as proof-of-principle by fluorescent microscopy and confirmed the specific binding of eGFP to mu B-cAbGFP4. Dynamic flow chamber studies demonstrated the ability of mu B-cAbVCAM1-5 to bind VCAM-1 in fast flow (up to 5 dynes/cm(2)). In vivo targeting studies were performed in MC38 tumor-bearing mice (n=4). mu B-cAbVCAM1-5 or control mu B-cAbGFP4 were injected intravenously and imaged using a contrast-specific ultrasound imaging mode. The echo intensity in the tumor was measured 10 min post-injection. mu B-cAbVCAM1-5 showed an enhanced signal compared to control mu Bs (p

Ook een kleine ophoping of ‘plaque’ tegen een bloedvatwand kan een infarct veroorzaken. Wetenschappers zoeken naar middelen om stabiele plaques die geen direct gevaar opleveren, te onderscheiden van tikkende tijdbommen.

The role of the extrinsic ligaments, together with the intrinsic ligaments, appears to be much more important than previously thought in the setting of carpal stability. The anatomy and pathology of the extrinsic wrist ligaments is complex. Magnetic resonance imaging (MRI) with thin slices is essential for visualization. This article describes the pathological appearance of the extrinsic palmar and dorsal radiocarpal and ulnocarpal ligaments on MRI, correlated with arthroscopy (performed by two skilled hand surgeons), clinical findings, and follow-up. High-resolution MRI, especially using isotropic three-dimensional sequences with orthogonal multiplanar reconstructions on 3T MR systems, allows detailed depiction of many of the extrinsic ligaments affected in carpal injuries. Recognition of ligament abnormalities is improved by intra-articular or intravenous injection of contrast before the examination. Both techniques may help to determine the precise localization, size, and extent of dorsal and palmar radiocarpal and ulnocarpal ligament lesions. Further experience with these techniques is needed to define the place of MRI in the management of traumatic wrist injuries.

Objectives The use of ionising radiation in medical imaging is accompanied with occupational exposure which should be limited by optimised room design and safety instructions. These measures can however not prevent that workers are exposed to instantaneous dose rates, e.g. the residual exposure through shielding or the exposure of discharged nuclear medicine patients. The latter elements are often questioned by workers and detailed assessment should give more information about the impact on the individual radiation dose. Methods Cumulated radiation exposure was measured in a university hospital during a period of 6 months by means of thermoluminescent dosimeters. Radiation exposure was measured at background locations and at locations where enhanced exposure levels are expected but where the impact on the individual exposure is unclear. Results The results show a normal distribution of the cumulated background radiation level. No enhanced cumulated radiation exposure which significantly differs from this background level could be found during the operation of intra-oral apparatus, during ultrasonography procedures among nuclear medicine patients and at operator consoles of most CT-rooms. Conclusions This 6 months survey offers useful information about occupational low level exposure in medical imaging and the findings can be useful in both risk communication and decision making.