An iterative algorithm for sparse and constrained recovery with applications to divergence-free current reconstructions in magneto-encephalography

We propose an iterative algorithm for the minimization of a $\ell_1$-norm penalized least squares functional, under additional linear constraints. The algorithm is fully explicit: it uses only matrix multiplications with the three matrices present in the problem (in the linear constraint, in the data misfit part and in penalty term of the functional). None of the three matrices must be invertible. Convergence is proven in a finite-dimensional setting. We apply the algorithm to a synthetic problem in magneto-encephalography where it is used for the reconstruction of divergence-free current densities subject to a sparsity promoting penalty on the wavelet coefficients of the current densities. We discuss the effects of imposing zero divergence and of imposing joint sparsity (of the vector components of the current density) on the current density reconstruction.Comment: 21 pages, 3 figure

Practical error estimates for sparse recovery in linear inverse problems

The effectiveness of using model sparsity as a priori information when solving linear inverse problems is studied. We investigate the reconstruction quality of such a method in the non-idealized case and compute some typical recovery errors (depending on the sparsity of the desired solution, the number of data, the noise level on the data, and various properties of the measurement matrix); they are compared to known theoretical bounds and illustrated on a magnetic tomography example.Comment: 11 pages, 5 figure

Mikrovaskuläre Rekonstruktion unter Einsatz von AV-Loops und arteriellen Interponaten bei Patienten mit Defekten im Kopf-Hals-Bereich

Objectives: Defect coverage of soft tissue defects in the head and neck area is a challenge, especially in case of a vessel-depleted neck. Flap transplantation using vascular reconstructions, such as an arterio-venous (AV) loop or a vein graft, is often the only therapeutic option. The aim of this study is to evaluate results in covering oncological defects with the help of vascular reconstructions and subsequent free flap transplantation as a combination procedure with particular regard to soft tissue defects in the head and neck area. Design and Methods: In context of this work, the data of nine patients treated with an AV loop or vein graft for arterial lengthening between 2007 and 2017 to cover defects in the head and neck area were analyzed retrospectively. Demographic data, comorbidities, surgical technique, hospitalization with a special focus on perioperative anticoagulation and transfusion, survival and flap function were also recorded. Observations and Results: Six out of nine patients included in this study received an AV loop, three a vein graft. The primary success rate was 78 %. Four out of six loops (67 %) and three vein grafts (100 %) were successful. On average, 15 erythrocyte concentrates (range, [2-38]) were transfused per stay. Postoperatively, anticoagulation was performed in three cases using a heparin perfusor with an aimed partial thromboplastin time of 60-80 seconds and in three cases using low molecular weight heparin (LMWH). Combined therapy with LMWH and a new oral anticoagulant, LMWH and acetylsalicylic acid or heparin perfusor and acetylsalicylic acid was performed for the remaining patients. At the moment there is no standardized procedure for postoperative anticoagulation after flap covering in the head and neck area. The survival rate of the observed patient group was 77.8 % after one year, 64.8 % after two years and 43.2 % after 30 months. Conclusions: There is no relationship between the number of erythrocyte concentrates consumed and the outcome of the flap transfer. However, the consumption of transfused blood is high. Anticoagulation is also not associated with the amount of complications. The combined therapy of vascular reconstruction with subsequent free flap transfer initially shows high complication rates and a high consumption of resources. Nevertheless, the use of an AV loop or vein graft enables a reconstruction with free flap transfer even in patients with a limited preoperative general condition, a vessel-depleted neck and serious soft tissue defects in the head and neck area.Hintergrund und Ziele: Die Defektdeckung bei Weichteildefekten im Kopf- und Halsbereich stellt eine Herausforderung dar, insbesondere, wenn passende Anschlussgefäße zum freien Lappentransfer im Defektareal fehlen. Als oftmals einzige therapeutische Behandlungsmaßnahme bleibt die Lappentransplantation mittels vaskulärer Rekonstruktionen, wie einem arteriovenösen (AV-) Loop oder einem Veneninterponat. Ziel dieser Arbeit ist die Auswertung der Ergebnisse von kombinierten Operationen zur Deckung onkologischer Defekte mit Hilfe vaskulärer Rekonstruktion und anschließender freier Lappentransplantation im Kopf- und Halsbereich. Methoden: Im Rahmen dieser Arbeit wurden die Daten von insgesamt neun Patienten retrospektiv analysiert, die zwischen 2007 und 2017 mit einem AV-Loop oder einem Interponat als Arterienverlängerung zur Defektdeckung im Kopf-Hals-Bereich versorgt wurden. Demografische Daten, Komorbiditäten, Operationstechnik, Krankenhausaufenthalt mit besonderem Hinblick auf die perioperative Antikoagulation und Transfusion, das Überleben und die Lappenfunktion wurden miterfasst. Ergebnisse: Sechs der in die Studie eingeschlossenen Patienten erhielten einen AV-Loop, drei ein arterielles Interponat. Es ergab sich eine primäre Erfolgsrate von 78 %. Dabei waren vier der Loops (67 %) und alle drei Veneninterponate (100 %) erfolgreich. Im Durchschnitt erfolgte eine Transfusion von 15 Erythrozytenkonzentraten (Bereich von 2-38) pro Aufenthalt. Postoperativ erfolgte die Antikoagulation mittels Heparin-Perfusor mit dem Ziel einer partiellen Thromboplastinzeit von 60-80 Sekunden in drei Fällen und mit niedermolekularem Heparin (LMWH) in drei Fällen. Bei den übrigen Patienten wurde jeweils eine kombinierte Therapie mit LMWH und einem neuen oralen Antikoagulans, LMWH und Acetylsalicylsäure (ASS) oder Heparin-Perfusor und ASS durchgeführt. Es existiert bisher kein standardisiertes Vorgehen bei der postoperativen Antikoagulation nach Lappendeckungen im Kopf-Hals-Bereich. Die Überlebensrate der beobachteten Patientengruppe lag nach einem Jahr bei 77,8 %, nach zwei Jahren bei 64,8 % und nach 30 Monaten bei 43,2 %. Schlussfolgerungen: Es zeigt sich kein Zusammenhang zwischen der Anzahl der verbrauchten Erythrozytenkonzentrate und dem Lappenverlust. Der Verbrauch an Blutkonserven ist allerdings hoch. Die Antikoagulation lässt sich ebenfalls nicht mit auftretenden Komplikationen in Verbindung bringen. Das kombinierte Therapieverfahren der Gefäßrekonstruktion mit anschließendem freien Lappentransfer zeigt initial eine hohe Komplikationsrate bei hohem Ressourcenverbrauch. Trotzdem ermöglicht der Einsatz eines AV-Loops oder Veneninterponats letztlich sogar bei Patienten mit eingeschränktem präoperativen Allgemeinzustand, kompromittierter Gefäßsituation und schwerwiegenden Weichteildefekten im Kopf-Hals-Bereich eine Rekonstruktion mit freiem Lappentransfer

Development of refractive errors - what can we learn from inherited retinal dystrophies?

PURPOSE: It is unknown which retinal cells are involved in the retina-to-sclera signaling cascade causing myopia. As inherited retinal dystrophies (IRD) are characterized by dysfunction of a single retinal cell type and have a high risk of refractive errors, a study investigating the affected cell type, causal gene and refractive error in IRDs may provide insight herein. DESIGN: Case-control study. METHODS: _Study population:_ 302 patients with IRD from two ophthalmogenetic centers in the Netherlands. _Reference population:_ population-based Rotterdam Study-III and ERF Study (N=5,550). Distributions and mean spherical equivalent (SE) were calculated for main affected cell type and causal gene; and risks of myopia and hyperopia were evaluated using logistic regression. RESULTS: Bipolar cell related dystrophies were associated with the highest risk of SE high myopia 239.7; OR mild hyperopia 263.2, both P<0.0001; SE -6.86 D [SD 6.38]); followed by cone dominated dystrophies (OR high myopia 19.5, P<0.0001; OR high hyperopia 10.7, P=0.033; SE -3.10 D [SD 4.49]); rod dominated dystrophies (OR high myopia 10.1, P<0.0001; OR high hyperopia 9.7, P=0.001; SE -2.27 D [SD 4.65]); and RPE related dystrophies (OR low myopia 2.7; P=0.001; OR high hyperopia 5.8; P=0.025; SE -0.10 D [SD 3.09]). Mutations in RPGR (SE -7.63 D [SD 3.31]) and CACNA1F (SE -5.33 D [SD 3.10]) coincided with the highest degree of myopia; in CABP4 (SE 4.81 D [SD 0.35]) with the highest degree of hyperopia. CONCLUSIONS: Refractive errors, in particular myopia, are common in IRD. The bipolar synapse, and the inner and outer segments of the photoreceptor may serve as critical sites for myopia development

Technical feasibility of [18F]FET and [18F]FAZA PET guided radiotherapy in a F98 glioblastoma rat model

Background: Glioblastoma (GB) is the most common primary malignant brain tumor. Standard medical treatment consists of a maximal safe surgical resection, subsequently radiation therapy (RT) and chemotherapy with temozolomide (TMZ). An accurate definition of the tumor volume is of utmost importance for guiding RT. In this project we investigated the feasibility and treatment response of subvolume boosting to a PET-defined tumor part. Method: F98 GB cells inoculated in the rat brain were imaged using T2- and contrast-enhanced T1-weighted (T1w) MRI. A dose of 20 Gy (5 x 5 mm(2)) was delivered to the target volume delineated based on T1w MRI for three treatment groups. Two of those treatment groups received an additional radiation boost of 5 Gy (1 x 1 mm(2)) delivered to the region either with maximum [F-18]FET or [F-18]FAZA PET tracer uptake, respectively. All therapy groups received intraperitoneal (IP) injections of TMZ. Finally, a control group received no RT and only control IP injections. The average, minimum and maximum dose, as well as the D-90-, D-50- and D-2- values were calculated for nine rats using both RT plans. To evaluate response to therapy, follow-up tumor volumes were delineated based on T1w MRI. Results: When comparing the dose volume histograms, a significant difference was found exclusively between the D-2-values. A significant difference in tumor growth was only found between active therapy and sham therapy respectively, while no significant differences were found when comparing the three treatment groups. Conclusion: In this study we showed the feasibility of PET guided subvolume boosting of F98 glioblastoma in rats. No evidence was found for a beneficial effect regarding tumor response. However, improvements for dose targeting in rodents and studies investigating new targeted drugs for GB treatment are mandatory

New fluoroethyl phenylalanine analogues as potential LAT1-targeting PET tracers for glioblastoma

Abstract The use of O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) as a positron emission tomography (PET) tracer for brain tumor imaging might have some limitations because of the relatively low affinity for the L-type amino acid transporter 1 (LAT1). To assess the stereospecificity and evaluate the influence of aromatic ring modification of phenylalanine LAT1 targeting tracers, six different fluoroalkylated phenylalanine analogues were synthesized. After in vitro Ki determination, the most promising compound, 2-[18F]-2-fluoroethyl-l-phenylalanine (2-[18F]FELP), was selected for further evaluation and in vitro comparison with [18F]FET. Subsequently, 2-[18F]FELP was assessed in vivo and compared with [18F]FET and [18F]FDG in a F98 glioblastoma rat model. 2-[18F]FELP showed improved in vitro characteristics over [18F]FET, especially when the affinity and specificity for system L is concerned. Based on our results, 2-[18F]FELP is a promising new PET tracer for brain tumor imaging

The Path Toward PET-Guided Radiation Therapy for Glioblastoma in Laboratory Animals: A Mini Review

Glioblastoma is the most aggressive and malignant primary brain tumor in adults. Despite the current state-of-the-art treatment, which consists of maximal surgical resection followed by radiation therapy, concomitant, and adjuvant chemotherapy, progression remains rapid due to aggressive tumor characteristics. Several new therapeutic targets have been investigated using chemotherapeutics and targeted molecular drugs, however, the intrinsic resistance to induced cell death of brain cells impede the effectiveness of systemic therapies. Also, the unique immune environment of the central nervous system imposes challenges for immune-based therapeutics. Therefore, it is important to consider other approaches to treat these tumors. There is a well-known dose-response relationship for glioblastoma with increased survival with increasing doses, but this effect seems to cap around 60 Gy, due to increased toxicity to the normal brain. Currently, radiation treatment planning of glioblastoma patients relies on CT and MRI that does not visualize the heterogeneous nature of the tumor, and consequently, a homogenous dose is delivered to the entire tumor. Metabolic imaging, such as positron-emission tomography, allows to visualize the heterogeneous tumor environment. Using these metabolic imaging techniques, an approach called dose painting can be used to deliver a higher dose to the tumor regions with high malignancy and/or radiation resistance. Preclinical studies are required for evaluating the benefits of novel radiation treatment strategies, such as PET-based dose painting. The aim of this review is to give a brief overview of promising PET tracers that can be evaluated in laboratory animals to bridge the gap between PET-based dose painting in glioblastoma patients

IMI-Management and Investigation of High Myopia in Infants and Young Children

The purpose of this study was to evaluate the epidemiology, etiology, clinical assessment, investigation, management, and visual consequences of high myopia (≤−6 diopters [D]) in infants and young children