Background-Transplantation of endothelial progenitor cells (EPCs) improves vascularization and left ventricular functionafter experimental myocardial ischemia. However, tissue distribution of transplanted EPCs has not yet been monitored in living animals. Therefore, we tested whether radioactive labeling allows us to detect injected EPCs. Methods and Results-Human EPCs were isolated from peripheral blood, characterized by expression of endothelial marker proteins, and radioactively labeled with [ 111 In]indium oxine. EPCs (10 6 ) were injected in athymic nude rats 24 hours after myocardial infarction (nϭ8) or sham operation (nϭ8). Scintigraphic images were acquired after 1, 24, 48, and 96 hours after EPC injection. Animals were then killed, and specific radioactivity was measured in different tissues. At 24 to 96 hours after intravenous injection of EPCs, Ϸ70% of the radioactivity was localized in the spleen and liver, with only Ϸ1% of the radioactivity identified in the heart of sham-operated animals. After myocardial infarction, the heart-to-muscle radioactivity ratio increased significantly, from 1.02Ϯ0.19 in sham-operated animals to 2.03Ϯ0.37 after intravenous administration of EPCs. Injection of EPCs into the left ventricular cavity increased this ratio profoundly, from 2.69Ϯ1.54 in sham-operated animals to 4.70Ϯ1.55 (PϽ0.05) in rats with myocardial infarction. Immunostaining of cryosections from infarcted hearts confirmed that EPCs homed predominantly to the infarct border zone. Conclusions-Although only a small proportion of radiolabeled EPCs are detected in nonischemic myocardium, myocardial infarction increases homing of transplanted EPCs in vivo profoundly. Radiolabeling might eventually provide an useful tool for monitoring the fate of transplanted progenitor cells and for clinical cell therapy. (Circulation.

ObjectiveThe purpose of this prospective multicenter study was to assess the safety and technical feasibility of volumetric Magnetic Resonance-guided High Intensity Focused Ultrasound (MR-HIFU) ablation for treatment of patients with symptomatic uterine fibroids.MethodsThirty-three patients with 36 fibroids were treated with volumetric MR-HIFU ablation. Treatment capability and technical feasibility were assessed by comparison of the Non-Perfused Volumes (NPVs) with MR thermal dose predicted treatment volumes. Safety was determined by evaluation of complications or adverse events and unintended lesions. Secondary endpoints were pain and discomfort scores, recovery time and length of hospital stay.ResultsThe mean NPV calculated as a percentage of the total fibroid volume was 21.7%. Correlation between the predicted treatment volumes and NPVs was found to be very strong, with a correlation coefficient r of 0.87. All patients tolerated the treatment well and were treated on an outpatient basis. No serious adverse events were reported and recovery time to normal activities was 2.3 ± 1.8 days.ConclusionThis prospective multicenter study proved that volumetric MR-HIFU is safe and technically feasible for the treatment of symptomatic uterine fibroids.Key Points• Magnetic-resonance-guided high intensity focused ultrasound allows non-invasive treatment of uterine fibroids.• Volumetric feedback ablation is a novel technology that allows larger treatment volumes• MR-guided ultrasound ablation of uterine fibroids appears safe using volumetric feedback

The discussed EE(⋆) method provides desirable features for image-based model calibration or hybrid image registration algorithms in which the model serves as a biophysical prior. This is due to (i) ease of implementation, (ii) low memory requirements, (iii) efficiency, (iv) a straightforward interface for parameter updates, and (v) the fact that the method is inherently matrix-free. The explicit time integration method is confirmed via experiments for automated model calibration. Qualitative and quantitative analysis demonstrates that the proposed framework allows for recovering observations in medical imaging data and by that phenomenological model validity.

Sonication accuracy of volumetric MR imaging-guided high-intensity focused ultrasound ablation of uterine fibroids appears clinically acceptable and may be further improved by feedback control to produce more consistent ablation zones.

Purpose: To evaluate a novel feedback-regulated volumetric sonication method in MR-guided HIFU treatment of symptomatic uterine fibroids. Materials and Methods: 27 fibroids with an average volume of 124.9???139.8 cc in 18 women with symptomatic uterine fibroids were ablated using the new HIFU system Sonalleve (1.5?T MR system Achieva, Philips). 21 myomas in 13 women were reevaluated 6 months later. Standard (treatment) cells (TC) and feedback-regulated (feedback) cells (FC) with a diameter of 4, 8, 12, and 16?mm were used and compared concerning sonication success, diameter of?induced necrosis, and maximum achieved temperature. The non-perfused volume ratio (NPV related to myoma volume) was quantified. The fibroid volume was measured before, 1 month, and 6 months after therapy. Symptoms were quantified using a specific questionnaire (UFS-QoL). Results: In total, 205 TC and 227 FC were applied. The NPV ratio was 23???15?% (2???55). The TC were slightly smaller than intended (?3.9???52?%; range, ?100???81), while the FC were 20.1???25.3?% bigger (p?=?0.02). Feedback mechanism is less diversifying in diameter (p?

Although ∼40% of patients with metastatic melanoma develop brain metastases, the presence of brain metastases often precludes enrolment in clinical trials for advanced melanoma. However, the development of symptomatic brain metastases markedly increases mortality. The antiprogrammed-death-receptor-1 antibody pembrolizumab achieves extracranial metastases disease response rates of up to 50%. Here, we report the rapid and sustained response of symptomatic multifocal brain metastases in a melanoma ipilimumab-pretreated patient under pembrolizumab, combined with high-dose dexamethasone therapy during the induction phase of therapy. Complete remission has been maintained for over 1 year of follow-up and has correlated with the response rate observed in the extracranial metastases. Radiological disease response was identified during the first follow-up visit in the absence of adjuvant radiotherapy. This report highlights the need for further clinical studies to specifically address the therapeutic potential of antiprogrammed-death-receptor-1 monotherapy in the management of untreated brain metastases in melanoma.

Uterine fibroids are the most common benign tumors in postmenopausal women which can cause severe symptoms and considerably reduce the quality of life. Patients are requesting minimally invasive, organ-saving therapies increasingly more often and magnetic resonance-guided focused ultrasound is a promising new technology which even surpasses these requirements as it is a totally non-invasive approach. The possibility of real-time temperature mapping allows a safe and precise thermal ablation of uterine fibroids. The rate of adverse events is low and safety and efficiency have been proven in several clinical studies. Further studies will have to be carried out to demonstrate long-term success and comparability to the established therapies and clarify if focused ultrasound is a safe treatment for women with the desire for future pregnancy. The MR-guided focused ultrasound technique is an effective and gentle treatment for uterine fibroids and holds a great potential for further indications.

Mitochondrial cytochrome P450 side-chain cleavage enzyme (P450scc, CYP11A1) is the initiating enzyme of steroidogenesis and converts cholesterol to pregnenolone. Here we describe neurological, cerebral magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) findings in a patient with a homozygous disruption of P450scc. Free γ-aminobutyric acid (GABA) and glutamate levels were measured in the patient's CSF and control samples from 10 subjects by mean of high performance liquid chromatography with electrochemical detection. In the CSF, patient's free GABA levels were significantly reduced in comparison to control values. Cerebral MRI revealed multiple supratentorial located T2 lesions in the periventricular and peritrigonal white matter without gadolinium enhancement or diffusion restriction of lesions. Both MRI and CSF neurotransmitter findings in our patient with P450scc deficiency were comparable to those found in multiple sclerosis.