In vivo visualization of cells labeled with superparamagnetic iron oxides by a sub-millisecond gradient echo sequence

Object: In vivo magnetic resonance imaging (MRI) of iron-labeled pancreatic islets (PIs) transplanted into the liver is still challenging in humans. The aim of this study was to develop and evaluate a double contrast method for the detection of PIs labeled with superparamagnetic iron oxide (SPIO) nanoparticles. Materials and methods: A double-echo three-dimensional (3D) spoiled gradient echo sequence was adapted to yield a sub-millisecond first echo time using variable echo times and highly asymmetric Cartesian readout. Positive contrast was achieved by conventional and relative image subtraction. Experiments for cell detection efficiency were performed in vitro on gelatin phantoms, in vivo on a Lewis rat and on a patient 6months after PI transplantation. Results: It was demonstrated that the proposed method can be used for the detection of transplanted PIs with positive contrast in vitro and in vivo. For all experiments, relative subtraction yielded comparable and in some cases better contrast than conventional subtraction. For the first time, positive contrast imaging of transplanted human PIs was performed in vivo in patients. Conclusion: The proposed method allows 3D data acquisition within a single breath-hold and yields enhanced contrast-to-noise ratios of transplanted SPIO labeled pancreatic islets relative to negative contrast images, therefore providing improved identification

Deep Anatomical Federated Network (Dafne): an open client/server framework for the continuous collaborative improvement of deep-learning-based medical image segmentation

Semantic segmentation is a crucial step to extract quantitative information from medical (and, specifically, radiological) images to aid the diagnostic process, clinical follow-up. and to generate biomarkers for clinical research. In recent years, machine learning algorithms have become the primary tool for this task. However, its real-world performance is heavily reliant on the comprehensiveness of training data. Dafne is the first decentralized, collaborative solution that implements continuously evolving deep learning models exploiting the collective knowledge of the users of the system. In the Dafne workflow, the result of each automated segmentation is refined by the user through an integrated interface, so that the new information is used to continuously expand the training pool via federated incremental learning. The models deployed through Dafne are able to improve their performance over time and to generalize to data types not seen in the training sets, thus becoming a viable and practical solution for real-life medical segmentation tasks.Comment: 10 pages (main body), 5 figures. Work partially presented at the 2021 RSNA conference and at the 2023 ISMRM conference In this new version: added author and change in the acknowledgmen

Muscle quantitative MRI as a novel biomarker in hereditary transthyretin amyloidosis with polyneuropathy: a cross-sectional study

BACKGROUND: The development of reproducible and sensitive outcome measures has been challenging in hereditary transthyretin (ATTRv) amyloidosis. Recently, quantification of intramuscular fat by magnetic resonance imaging (MRI) has proven as a sensitive marker in patients with other genetic neuropathies. The aim of this study was to investigate the role of muscle quantitative MRI (qMRI) as an outcome measure in ATTRv. METHODS: Calf- and thigh-centered multi-echo T2-weighted spin-echo and gradient-echo sequences were obtained in patients with ATTRv amyloidosis with polyneuropathy (n = 24) and healthy controls (n = 12). Water T2 (wT2) and fat fraction (FF) were calculated. Neurological assessment was performed in all ATTRv subjects. Quantitative MRI parameters were correlated with clinical and neurophysiological measures of disease severity. RESULTS: Quantitative imaging revealed significantly higher FF in lower limb muscles in patients with ATTRv amyloidosis compared to controls. In addition, wT2 was significantly higher in ATTRv patients. There was prominent involvement of the posterior compartment of the thighs. Noticeably, FF and wT2 did not exhibit a length-dependent pattern in ATTRv patients. MRI biomarkers correlated with previously validated clinical outcome measures, Polyneuropathy Disability scoring system, Neuropathy Impairment Score (NIS) and NIS-lower limb, and neurophysiological parameters of axonal damage regardless of age, sex, treatment and TTR mutation. CONCLUSIONS: Muscle qMRI revealed significant difference between ATTRv and healthy controls. MRI biomarkers showed high correlation with clinical and neurophysiological measures of disease severity making qMRI as a promising tool to be further investigated in longitudinal studies to assess its role at monitoring onset, progression, and therapy efficacy for future clinical trials on this treatable condition

Exploring T*2 decay : new methods for short echo time imaging and fat-water quantification

The major advantage of magnetic resonance imaging (MRI) over other imaging modalities like computed tomography (CT) is that it does not utilize ionizing radiation. A drawback of MRI in comparison to CT is that in general it requires longer scan times and for this reason fast scanning techniques have been proposed. Fast MR imaging can refer to fast scan times or fast signal acquisition. The first is important in various cases such as in abdominal scans to decrease motion sensitivity, while short echo times and short acquisition times allow visualization of tissues with fast signal relaxation. One category of MR sequences that allows fast scanning is gradient echo sequences. These sequences do not use radiofrequency pulses to yield a signal echo and this allows fast imaging, shorter echo times and scan times, while the signal decays according to the apparent transverse relaxation T_{2}^{*} . Gradient echo sequences can be used both for qualitative and quantitative imaging and during this thesis an application in each direction was explored. The first part of this thesis is related to fast gradient echo imaging for qualitative imaging of fast decaying signals. It is focused on the development of a short echo time sequence that can be easily translated to clinical settings. In the first chapter of this part a novel short echo time sequence is being introduced. Subsequently, two different applications are being discussed. Firstly, the application of the sequence to musculoskeletal imaging at high and ultra-high field is being described. In the second chapter, the effect of fat suppression on short T_{2} tissues imaging is being considered. At the last chapter of this part the sequence is adapted to be used for molecular imaging of iron oxide labeled cells. The second part of this thesis refers to quantitative gradient echo imaging. The aim is tissue characterization based on the analysis of the signal decay. A multi-echo sequence is adapted in order to be used with a novel powerful fitting tool for three-dimensional (3D) liver fat-water imaging. Preliminary results are presented from a comparison with a standard two-point Dixon technique

Open Science: Principles and Practices for Better Research

Material for journal club/seminar series at University of Basel

Integrated active tracking detector for MRI-guided interventions

We present a fully integrated detector suitable for active tracking of interventional devices in MR-guided interventions. The single-chip microsystem consists of a detection coil, a tuning capacitor, an intermediate frequency downconversion receiver, and a phase-locked-loop-based frequency synthesizer. Thanks to the integrated mixer, the chip output stage delivers an analog frequency-downconverted NMR signal in the frequency range from 0 to 200 kHz. The microchip, realized in a standard complementary metal oxide semiconductor technology, has a size of 1 x 2 x 0.74 mm3 and operates at a frequency of 63 MHz (i.e., in 1.5 T clinical scanners). Tests in a standard clinical scanner demonstrate the compatibility of the complementary metal oxide semiconductor microchip with clinical MRI systems. Using a solid sample of cis-polyisoprene having a size of 1 x 1.9 x 0.8 mm3 as internal signal source, the detector achieves a three-dimensional isotropic spatial resolution of 0.15 mm in a measuring time of 100 ms. Magn Reson Med, 2011. (C) 2011 Wiley-Liss, Inc

On the construction of a 3D-printed brain phantom as gold standard for the validation of brain segmentations

Background: In Multiple Sclerosis, quantification of the volume of brain structures in images acquired by magnetic resonance imaging (MRI) is a basic method involved in the assessment of structural abnormalities or in monitoring disease progression. However, tissue segmentation algorithms in MRI lack a ground truth for efficient and reliable validation. Aim: The aim of this study is to develop a realistic 3D-printed brain phantom to facilitate the development and validation of brain segmentation algorithms. Methods: The phantom was built in three stages. First, white matter (WM) and grey matter (GM) T1 intensities were derived from T1 relaxation maps of a healthy subject acquired in a 3T MRI scanner using an inversion recovery spin echo sequence. For mimicking WM and GM intensities, 0.6% agar gel samples with different concentrations of the contrast medium manganese chloride (MnCl2) were prepared. Moreover, 10 mg/mL 1% paraben was added as antimicrobial agent. At a second stage, to resemble the complex 3D geometry of the brain, WM and GM surface meshes were automatically extracted from an isotropic MPRAGE scan of the same subject. Extracted surfaces were then 3D-printed using polylactic acid thermoplastic and covered by a brushable silicone rubber to obtain flexible molds. At the last stage, the different parts of the phantom were assembled: the WM gel was injected into the WM surface mold; once the gel set, the mold was removed, a hydrophobic varnish layer was applied, and the GM mold was positioned on top; finally the GM gel was injected and the corresponding mold was pulled off when the gel became solid. Results: All the steps described were completed and the brain phantom was successfully constructed. T1 values calculated in the healthy subject (WM: 748.7 ± 13.0ms; GM: 1306.9 ± 76.5ms) were achieved using 0.12mM (WM gel: 842.0 ± 32.9ms) and 0.04 mM (GM gel: 1250.9 ± 65.3ms) of MnCl2, respectively. By means of the silicone molds, the folding patterns typical of WM and GM were reproduced, showing a high similarity with the real counterpart. Moreover, the thin layer of varnish added between tissues reduced the diffusion of the gels without creating a distinguishable interface. Discussion and conclusions: The described procedure enabled us to construct the first anthropomorphic brain phantom that can in the future be used for efficiently evaluating the performance of different MRI brain segmentation algorithms

Combining phase images from array coils using a short echo time reference scan (COMPOSER)

Purpose: To develop a simple method for combining phase images from multichannel coils that does not require a reference coil and does not entail phase unwrapping, fitting or iterative procedures. Theory and Methods: At very short echo time, the phase measured with each coil of an array approximates to the phase offset to which the image from that coil is subject. Subtracting this information from the phase of the scan of interest matches the phases from the coils, allowing them to be combined. The effectiveness of this approach is quantified in the brain, calf and breast with coils of diverse designs. Results: The quality of phase matching between coil elements was close to 100% with all coils assessed even in regions of low signal. This method of phase combination was similar in effectiveness to the Roemer method (which needs a reference coil) and was superior to the rival reference-coil-free approaches tested. Conclusion: The proposed approach—COMbining Phase data using a Short Echo-time Reference scan (COMPOSER)—is a simple and effective approach to reconstructing phase images from multichannel coils. It requires little additional scan time, is compatible with parallel imaging and is applicable to all coils, independent of configuration. Magn Reson Med 77:318–327, 2017

T1- and T2*-Mapping for Assessment of Tendon Tissue Biophysical Properties: A Phantom MRI Study

OBJECTIVES The aim of this study was to quantitatively assess changes in collagen structure using MR T1- and T2*-mapping in a novel controlled ex vivo tendon model setup. MATERIALS AND METHODS Twenty-four cadaveric bovine flexor tendons underwent MRI at 3 T before and after chemical modifications, representing mechanical degeneration and augmentation. Collagen degradation (COL), augmenting collagen fiber cross-linking (CXL), and a control (phosphate-buffered saline [PBS]) were examined in experimental groups, using histopathology as standard of reference. Variable echo-time and variable-flip angle gradient-echo sequences were used for T2*- and T1-mapping, respectively. Standard T1- and T2-weighted spin-echo sequences were acquired for visual assessment of tendon texture. Tendons were assessed subsequently for their biomechanical properties and compared with quantitative MRI analysis. RESULTS T1- and T2*-mapping was feasible and repeatable for untreated (mean, 545 milliseconds, 2.0 milliseconds) and treated tendons. Mean T1 and T2* values of COL, CXL, and PBS tendons were 1459, 934, and 1017 milliseconds, and 5.5, 3.6, and 2.5 milliseconds, respectively. T2* values were significantly different between enzymatically degraded tendons, cross-linked tendons, and controls, and were significantly correlated with mechanical tendon properties (r = -0.74, P < 0.01). T1 values and visual assessment could not differentiate CXL from PBS tendons. Photo-spectroscopy showed increased autofluorescence of cross-linked tendons, whereas histopathology verified degenerative lesions of enzymatically degraded tendons. CONCLUSIONS T2*-mapping has the potential to detect and quantify subtle changes in tendon collagen structure not visible on conventional clinical MRI. Tendon T2* values might serve as a biomarker for biochemical alterations associated with tendon pathology