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Using the inverse-electron-demand Diels Alder reaction we demonstrated non-invasive pretargeted tumor imaging in mice bearing LS174T colorectal xenografts. Anti-TAG72 mAb CC49 functionalized with trans-cyclooctene moieties was administered, followed 24 h later by 111In-labeled tetrazine. Pronounced tumor uptake of the 111In-tetrazine was demonstrated by SPECT/CT imaging of live mice up to 3 h post injection (tumor-to-muscle ratio: 13.1), while no tumor binding occurred in mice treated with unmodified CC49. The components exhibited a remarkable 52-57 % chemical reaction yield in mice. We are currently optimizing this system for cancer therapy.

This paper presents a top-down approach to construct execution views of a large and complex software intensive system. Execution viewsdescribe what the software does at runtime and how it does it. The presented approach represents a reverse architecting solution that follows a set of pre-defined viewpoints and a metamodel, which capturethe runtime perspective on a system of a particular development organization. It applies a dynamic analysis technique to extract runtime information from a combination of system logging and runtime measurements in a top-down fashion. The approach was developed and validated constructing execution views for an MRI system, thus it represent a solution that can be applied on similar large and complex software-intensive systems.

Several self-navigation techniques have been proposed to improve respiratory motion compensation in CMRA. In this work we implemented a2D self-navigation method by using the dummy profiles of a whole-heart balanced Steady-State Free Precession (bSSFP) sequence, which are primarily used to catalyze the magnetization towards the steady-state. To create 2D self-navigation images (2DSN), we added phase encoding gradients to the dummy profiles. With this approach we calculated foot-head (FH) and left-right (LR) motion and performed retrospective translational motion correction. Ten dummy profiles were acquired in each shot to create a 2DSN. 9 healthy subjects were scanned, and the proposed method was compared to conventional 1D self-navigation (1DSN) methods with FH correction by only considering the ky0-profile. FH correction was also performed with the diaphragmatic 1D pencil beam navigator (1Dnav) using a tracking factor of 0.6. 2DSN shows improved motion correction compared to 1DSN and 1Dnav for all coronary arteries and all subjects for the investigated diaphragmatic gating window of 10 mm.

In social sciences such as psychiatry and psychology the use of objective measurement devices, let alone high tech equipment, is still rare. Psychiatric diagnostic processes are still depending heavily onthe observations, experience, and skills of a diagnosing psychiatrist or psychologist, which are sometimes backed up by the uses of (paper-and-pencil) tests. Of course, the rise of neuroimaging techniques such as EEG, CAT, MRI and fMRI have enormously increased the possibilities to objectively study brain anomalies in psychiatric patients, but nevertheless, establishing a psychiatric diagnosis is still mainly based on the (behavioural) criteria described in DSM-IV, whichhave to be observed and assessed by a human diagnostician. Many ofthe major challenges of mental health care, however, are not dealingwith the specific diagnostic categories presented in the DSM-IV, but with the behavioural manifestations and problem behaviours that stem from these psychiatric illnesses. Aggressive and disruptive behaviour, for instance, are the main causes for involuntary psychiatricadmissions, even though aggressive behaviour is not a specific diagnostic category in the DSM-IV. Nevertheless, psychiatric professionals are expected to be able to ‘predict’ dangerousness and violence risks of individual psychiatric patients, for instance when having tojudge about the necessity of forced pharmacological treatment, involuntary admissions, or the whether it is safe enough to discharge a patient. In other words, they make these assessments about risks of aggressive behavior, without it being an official psychiatric illness in terms of the DSM-IV, and without having access to measurement tools or equipment that can assess a state of physiological hyper arousal, let alone an assessment that can objectively ‘predict’ imminent aggression.

A Simultaneous Non-contrast Angiography and intraPlaque hemorrhage (SNAP) MR imaging technique was proposed to detect both luminal stenosis and hemorrhage in atherosclerosis patients in a single scan. 13patients with diagnosed carotid atherosclerotic plaque were recruited after informed consent. All scans were performed on a 3T MR imaging system with SNAP, 2D time-of-flight (TOF) and magnetization-prepared 3D rapid acquisition gradient echo (MP-RAGE) sequences. The SNAPsequence utilized a phase sensitive acquisition, and was designed toprovide positive signals corresponding to intraplaque hemorrhage (IPH) and negative signals corresponding to lumen. SNAP images were compared to TOF images to validate lumen area measurements using linear mixed models and the intraclass correlation coefficient (ICC). IPHidentification accuracy was evaluated by comparing to MP-RAGE images using Cohen’s Kappa. Diagnostic quality SNAP images were generatedfrom all subjects. Quantitatively, the lumen area measurements by SNAP were strongly correlated (ICC=0.96, p<0.001) with those measuredby TOF. For IPH detection, strong agreement (&#954;=0.82, p<0.001)was also identified between SNAP and MP-RAGE images. The SNAP technique was proposed and validated to reliably detect in a single acquisition both luminal size and intraplaque hemorrhage in the patients with carotid atherosclerosis.

Chemical exchange saturation transfer (CEST) based in vivo detectionand quantification of endogenous macro-molecules (i.e., amide proton transfer, APT) or exogenous contrast agents is a highly sensitivemolecular MRI technique bearing a substantial clinical potential forexample in oncology or for cerebro-vascular applications. Techniques for APT/CEST MRI on clinical MRI scanners are reviewed. Typical limitations arise from hardware specifications of the radio-frequency(RF) source(s) regarding maximum pulse length or RF duty-cycle as well as limits imposed by regulations on specific absorption rates (SAR). Clinical APT/CEST techniques described in the literature are compared to two novel approaches: (i) sequences based on operating thescanner in a mode provided for MRS proton-decoupling, and (ii), sequences based on the alternated use of the independent RF amplifiers within an MR system equipped with parallel RF transmission. In emerging applications in the area of whole-body MRI, sensitivity of the APT/CEST techniques to physiological motion is of particular concern.A respiratory triggered sequence is presented and feasibility is shown in the healthy human kidney (in collaboration with Sherry AD et al., UTSW, USA) in the context of CEST-pH mapping using Iopamidol (Bracco Inc., Italy) as contrast agent and ratiometric CEST signal analysis for an absolute pH measurement.

We describe a novel, minimally invasive laser technology for skin rejuvenation by creating isolated microscopic lesions within tissue below the epidermis using laser induced optical breakdown. Using an in-house built prototype device, tightly focused near-infrared laser pulses are used to create optical breakdown in the dermis while leaving the epidermis intact, resulting in lesions due to cavitation andplasma explosion. This stimulates a natural healing response and consequently skin remodeling, resulting in skin rejuvenation effects. Analysis of ex-vivo and in-vivo treated human skin samples successfully demonstrated the safety and effectiveness of the microscopic lesion creation inside the dermis. Treatments led to mild side effects that can be controlled by small optimizations of the optical skin contact and treatment depth within the skin. The histological results from a limited panel test performed on five test volunteers show evidence of microscopic lesion creation and new collagen formation at the sites of the optical breakdown. This potentially introduces a safe, breakthrough treatment procedure for skin rejuvenation without damaging the epidermis with no or little social down-time and with efficacy comparable to conventional fractional ablative techniques.

Preferred chroma enhancement and its dependence on hue were studiedin a two-part experiment using a wide-gamut multi-primary display.This builds on earlier experiments which showed a clear hue dependence but were limited by the gamut of the display they employed. In the first part of this experiment, a tuning task was used to refine the preference for chroma boost starting with standard-gamut (Rec. 709) images. The overall median preferred boost is roughly 20%, but it is not uniform over hues: preferred boost for orange, yellow, green, and cyan colors is greater than that for blue, magenta, and redcolors. Dependence on image content and observer was noted, thougha content-independent chroma boost created by aggregating preferenceover many images performs well, on average. An adjustment parameterfor overall chroma which incorporates the hue dependent chroma boost result averaged over image content should be sufficient to handlethe vast majority of inter-observer variance in preference. In thesecond part of the experiment, through a paired comparison task, theprescribed hue-dependent chroma boost was preferred over all othervariations, and all hue-preserving chroma boost variations were preferred over both colorimetrically accurate and naive same-drive-signal renderings. The results may be applied to display design to select gamut boundaries that maximize satisfaction over the observer population.