Low field slice-selective ZTE imaging of ultra-short [Formula: see text] tissues based on spin-locking.

Magnetic Resonance Imaging of hard biological tissues is very challenging due to small proton abundance and ultra-short [Formula: see text] decay times, especially at low magnetic fields, where sample magnetization is weak. While several pulse sequences, such as Ultra-short Echo Time (UTE), Zero Echo Time (ZTE) and SWeep Imaging with Fourier Transformation (SWIFT), have been developed to cope with ultra-short lived MR signals, only the latter two hold promise of imaging tissues with sub-millisecond [Formula: see text] times at low fields. All these sequences are intrinsically volumetric, thus 3D, because standard slice selection using a long soft radio-frequency pulse is incompatible with ultra-short lived signals. The exception is UTE, where double half pulses can perform slice selection, although at the cost of doubling the acquisition time. Here we demonstrate that spin-locking is a versatile and robust method for slice selection for ultra-short lived signals, and present three ways of combining this pulse sequence with ZTE imaging of the selected slice. With these tools, we demonstrate slice-selected 2D ex vivo imaging of the hardest tissues in the body at low field (260 mT) within clinically acceptable times.

Experimental validation of a rodent PET scanner prototype based on a single LYSO crystal tube.

Improving sensitivity and spatial resolution in small animal Positron Emission Tomography imaging instrumentation constitutes one of the main goals of nuclear imaging research. These parameters are degraded by the presence of gaps between the detectors. The present manuscript experimentally validates our prototype of an edge-less pre-clinical PET system based on a single LYSO:Ce annulus with an inner diameter of 62 mm and 10 outer facets of 26 × 52 mm2. Scintillation light is read out by arrays of 8 × 8 SiPMs coupled to the facets, using a projection readout of the rows and columns signals. The readout provides accurate Depth of Interaction (DOI). We have implemented a calibration that mitigates the DOI-dependency of the transaxial and axial impact coordinates, and the energy photopeak gain. An energy resolution of 23.4 ± 1.8% was determined. Average spatial resolution of 1.4 ± 0.2 and 1.3 ± 0.4 mm FWHM were achieved for the radial and axial directions, respectively. We found a peak sensitivity of 3.8% at the system center, and a maximum NECR at 40.6 kcps for 0.27 mCi. The image quality was evaluated using reconstructed images of an array of sources and the NEMA image quality phantom was also studied.

Portable magnetic resonance imaging of patients indoors, outdoors and at home.

Mobile medical imaging devices are invaluable for clinical diagnostic purposes both in and outside healthcare institutions. Among the various imaging modalities, only a few are readily portable. Magnetic resonance imaging (MRI), the gold standard for numerous healthcare conditions, does not traditionally belong to this group. Recently, low-field MRI technology companies have demonstrated the first decisive steps towards portability within medical facilities and vehicles. However, these scanners' weight and dimensions are incompatible with more demanding use cases such as in remote and developing regions, sports facilities and events, medical and military camps, or home healthcare. Here we present in vivo images taken with a light, small footprint, low-field extremity MRI scanner outside the controlled environment provided by medical facilities. To demonstrate the true portability of the system and benchmark its performance in various relevant scenarios, we have acquired images of a volunteer's knee in: (i) an MRI physics laboratory; (ii) an office room; (iii) outside a campus building, connected to a nearby power outlet; (iv) in open air, powered from a small fuel-based generator; and (v) at the volunteer's home. All images have been acquired within clinically viable times, and signal-to-noise ratios and tissue contrast suffice for 2D and 3D reconstructions with diagnostic value. Furthermore, the volunteer carries a fixation metallic implant screwed to the femur, which leads to strong artifacts in standard clinical systems but appears sharp in our low-field acquisitions. Altogether, this work opens a path towards highly accessible MRI under circumstances previously unrealistic.

Prepolarized MRI of hard tissues and solid-state matter.

Prepolarized MRI (PMRI) is a long-established technique conceived to counteract the loss in signal-to-noise ratio (SNR) inherent to low-field MRI systems. When it comes to hard biological tissues and solid-state matter, PMRI is severely restricted by their ultra-short characteristic relaxation times. Here we demonstrate that efficient hard-tissue prepolarization is within reach with a special-purpose 0.26 T scanner designed for ex vivo dental MRI and equipped with suitable high-power electronics. We have characterized the performance of a 0.5 T prepolarizer module, which can be switched on and off in 200 µs. To this end, we have used resin, dental and bone samples, all with T1 times of the order of 20 ms at our field strength. The measured SNR enhancement is in good agreement with a simple theoretical model, and deviations in extreme regimes can be attributed to mechanical vibrations due to the magnetic interaction between the prepolarization and main magnets.

Magneto-stimulation limits in medical imaging applications with rapid field dynamics.

Objective.The goal of this work is to extend previous peripheral nerve stimulation (PNS) studies to scenarios relevant to magnetic particle imaging (MPI) and low-field magnetic resonance imaging (MRI), where field dynamics can evolve at kilo-hertz frequencies.Approach.We have constructed an apparatus for PNS threshold determination on a subject's limb, capable of narrow and broad-band magnetic stimulation with pulse characteristic times down to 40µs.Main result.From a first set of measurements on 51 volunteers, we conclude that the PNS dependence on pulse frequency/rise-time is compatible with traditional stimulation models where nervous responses are characterized by a rheobase and a chronaxie. Additionally, we have extended pulse length studies to these fast timescales and confirm thresholds increase significantly as trains transition from tens to a few pulses. We also look at the influence of field spatial distribution on PNS effects, and find that thresholds are higher in an approximately linearly inhomogeneous field (relevant to MRI) than in a rather homogeneous distribution (as in MPI).Significance.PNS constrains the clinical performance of MRI and MPI systems. Extensive magneto-stimulation studies have been carried out recently in the field of MPI, where typical operation frequencies range from single to tens of kilo-hertz. However, PNS literature is scarce for MRI in this fast regime, relevant to small (low inductance) dedicated MRI setups, and where the resonant character of MPI coils prevents studies of broad-band stimulation pulses. This work advances in this direction.

Numerical Study of Acoustic Holograms for Deep-Brain Targeting through the Temporal Bone Window.

Acoustic holograms can encode complex wavefronts to compensate the aberrations of a therapeutical ultrasound beam propagating through heterogeneous tissues such as the skull, and simultaneously, they can generate diffraction-limited acoustic images, that is, arbitrary shaped focal spots. In this work, we numerically study the performance of acoustic holograms focusing at the thalamic nuclei when the source is located at the temporal bone window. The temporal window is the thinnest area of the lateral skull and it is mainly hairless, so it is a desirable area through which to transmit ultrasonic waves to the deep brain. However, in targeting from this area the bilateral thalamic nuclei are not aligned with the elongated focal spots of conventional focused transducers, and in addition, skull aberrations can distort the focal spot. We found that by using patient-specific holographic lenses coupled to a single-element 650-kHz-frequency 65-mm-aperture source, the focal spot can be sharply adapted to the thalamic nuclei in a bilateral way while skull aberrations are mitigated. Furthermore, the performance of these holograms was studied under misalignment errors between the source and the skull, concluding that for misalignments up to 5°, acoustic images are correctly restored. This work paves the way to designing clinical applications of transcranial ultrasound such as blood-brain barrier opening for drug delivery or deep-brain neuromodulation using this low-cost and personalized technology, presenting desirable aspects for long-term treatments because the patient's head does not need to be shaved completely and skull heating is low.

Timing evaluation of a PET detector block based on semi-monolithic LYSO crystals.

PURPOSE: Detectors for positron emission tomography (PET) typically use two types of scintillation crystals, pixelated or monolithic. A variant of these types of scintillators are the so-called semi-monolithic crystals. They consist of a monolithic crystal segmented in one direction in pieces called slabs. These scintillators have the potential to successfully combine the benefits of pixelated and monolithic configurations, providing good timing and spatial resolutions as well as the capacity to decode the depth of interaction (DOI) information. In this work, the timing performance of a detector based on semi-monolithic crystals was studied in depth. The energy response was also evaluated. METHODS: The semi-monolithic detector consists of 1 × 24 LYSO slabs of 25.4 × 12 × 0.95 mm3 each. The bottom surface of the slabs is coupled to an array of 8 × 8 silicon photomultipliers (SiPMs) of 3 × 3 mm2 active area, 50 µm cell size and 3.2 mm pitch. The 64 output signals were independently readout by the TOFPET2 ASIC. In order to achieve the best coincidence time resolution (CTR), four different time walk corrections were tested. Additional work investigated the best method of combining the timestamps belonging to the same event. RESULTS: The resolvability of the slabs in the measured flood maps improves with the thickness of a light guide placed in between the scintillators and photosensors. The energy resolution does not change significantly with values as good as 13.7%. Regarding the CTR, values of 335.8, 363, 369.8, and 402.5 ps have been obtained for the whole detector for no light guide, 0.5, 1.0, and 1.5 mm thickness light guide cases, respectively. These values further improve to 276.1, 302.6, 305.6 and 336.2 ps, respectively, when energy-weighted averaging of timestamps is applied. CONCLUSIONS: We have shown both an excellent timing resolution and good energy resolution for a PET detector based on semi-monolithic crystals. The use of light guides of different thicknesses does not significantly affect the energy resolution of the whole detector, but the timing capabilities slightly worsen with the increasing thickness of the light guide.

Architecture-Level Optimization on Digital Silicon Photomultipliers for Medical Imaging.

Silicon photomultipliers (SiPMs) are arrays of single-photon avalanche diodes (SPADs) connected in parallel. Analog silicon photomultipliers are built in custom technologies optimized for detection efficiency. Digital silicon photomultipliers are built in CMOS technology. Although CMOS SPADs are less sensitive, they can incorporate additional functionality at the sensor plane, which is required in some applications for an accurate detection in terms of energy, timestamp, and spatial location. This additional circuitry comprises active quenching and recharge circuits, pulse combining and counting logic, and a time-to-digital converter. This, together with the disconnection of defective SPADs, results in a reduction of the light-sensitive area. In addition, the pile-up of pulses, in space and in time, translates into additional efficiency losses that are inherent to digital SiPMs. The design of digital SiPMs must include some sort of optimization of the pixel architecture in order to maximize sensitivity. In this paper, we identify the most relevant variables that determine the influence of SPAD yield, fill factor loss, and spatial and temporal pile-up in the photon detection efficiency. An optimum of 8% is found for different pixel sizes. The potential benefits of molecular imaging of these optimized and small-sized pixels with independent timestamping capabilities are also analyzed.

Simultaneous imaging of hard and soft biological tissues in a low-field dental MRI scanner.

Magnetic Resonance Imaging (MRI) of hard biological tissues is challenging due to the fleeting lifetime and low strength of their response to resonant stimuli, especially at low magnetic fields. Consequently, the impact of MRI on some medical applications, such as dentistry, continues to be limited. Here, we present three-dimensional reconstructions of ex-vivo human teeth, as well as a rabbit head and part of a cow femur, all obtained at a field strength of 260 mT. These images are the first featuring soft and hard tissues simultaneously at sub-Tesla fields, and they have been acquired in a home-made, special-purpose, pre-medical MRI scanner designed with the goal of demonstrating dental imaging at low field settings. We encode spatial information with two pulse sequences: Pointwise-Encoding Time reduction with Radial Acquisition and a new sequence we have called Double Radial Non-Stop Spin Echo, which we find to perform better than the former. For image reconstruction we employ Algebraic Reconstruction Techniques (ART) as well as standard Fourier methods. An analysis of the resulting images shows that ART reconstructions exhibit a higher signal-to-noise ratio with a more homogeneous noise distribution.

Pilot performance of a dedicated prostate PET suitable for diagnosis and biopsy guidance.

BACKGROUND: Prostate cancer (PCa) represents one of the most common types of cancers facing the male population. Nowadays, to confirm PCa, systematic or multiparametric MRI-targeted transrectal or transperineal biopsies of the prostate are required. However, due to the lack of an accurate imaging technique capable to precisely locate cancerous cells in the prostate, ultrasound biopsies sample random parts of the prostate and, therefore, it is possible to miss regions where those cancerous cells are present. In spite of the improvement with multiparametric MRI, the low reproducibility of its reading undermines the specificity of the method. Recent development of prostate-specific radiotracers has grown the interest on using positron emission tomography (PET) scanners for this purpose, but technological improvements are still required (current scanners have resolutions in the range of 4-5 mm). RESULTS: The main goal of this work is to improve state-of-the-art PCa imaging and diagnosis. We have focused our efforts on the design of a novel prostate-dedicated PET scanner, named ProsPET. This system has small scanner dimensions defined by a ring of just 41 cm inner diameter. In this work, we report the design, implementation, and evaluation (both through simulations and real data) of the ProsPET scanner. We have been able to achieve < 2 mm resolution in reconstructed images and high sensitivity. In addition, we have included a comparison with the Philips Gemini-TF scanner, which is used for routine imaging of PCa patients. The ProsPET exhibits better contrast, especially for rod sizes as small as 4.5 mm in diameter. Finally, we also show the first reconstructed image of a PCa patient acquired with the ProsPET. CONCLUSIONS: We have designed and built a prostate specific PET system, with a small footprint and improved spatial resolution when compared to conventional whole-body PET scanners. The gamma ray impact within each detector block includes accurate DOI determination, correcting for the parallax error. The potential role of combined organ-dedicated prostate-specific membrane antigen (PSMA) PET and ultrasound devices, as a prebiopsy diagnostic tool, could be used to guide sampling of the most aggressive sites in the prostate.

Exploring TOF capabilities of PET detector blocks based on large monolithic crystals and analog SiPMs.

Monolithic scintillators are more frequently used in PET instrumentation due to their advantages in terms of accurate position estimation of the impinging gamma rays both planar and depth of interaction, their increased efficiency, and expected timing capabilities. Such timing performance has been studied when those blocks are coupled to digital photosensors showing an excellent timing resolution. In this work we study the timing behaviour of detectors composed by monolithic crystals and analog SiPMs read out by an ASIC. The scintillation light spreads across the crystal towards the photosensors, resulting in a high number of SiPMs and ASIC channels fired. This has been studied in relation with the Coincidence Timing Resolution (CTR). We have used LYSO monolithic blocks with dimensions of 50 × 50 × 15 mm3 coupled to SiPM arrays (8 × 8 elements with 6 × 6 mm2 area) which compose detectors suitable for clinical applications. While a CTR as good as 186 ps FWHM was achieved for a pair of 3 × 3 × 5 mm3 LYSO crystals, when using the monolithic block and the SiPM arrays, a raw CTR over 1 ns was observed. An optimal timestamp assignment was studied as well as compensation methods for the time-skew and time-walk errors. This work describes all steps followed to improve the CTR. Eventually, an average detector time resolution of 497 ps FWHM was measured for the whole thick monolithic block. This improves to 380 ps FWHM for a central volume of interest near the photosensors. The timing dependency with the photon depth of interaction and planar position are also included.

Generating Bessel beams with broad depth-of-field by using phase-only acoustic holograms.

We report zero-th and high-order acoustic Bessel beams with broad depth-of-field generated using acoustic holograms. While the transverse field distribution of Bessel beams generated using traditional passive methods is correctly described by a Bessel function, these methods present a common drawback: the axial distribution of the field is not constant, as required for ideal Bessel beams. In this work, we experimentally, numerically and theoretically report acoustic truncated Bessel beams of flat-intensity along their axis in the ultrasound regime using phase-only holograms. In particular, the beams present a uniform field distribution showing an elongated focal length of about 40 wavelengths, while the transverse width of the beam remains smaller than 0.7 wavelengths. The proposed acoustic holograms were compared with 3D-printed fraxicons, a blazed version of axicons. The performance of both phase-only holograms and fraxicons is studied and we found that both lenses produce Bessel beams in a wide range of frequencies. In addition, high-order Bessel beam were generated. We report first order Bessel beams that show a clear phase dislocation along their axis and a vortex with single topological charge. The proposed method may have potential applications in ultrasonic imaging, biomedical ultrasound and particle manipulation applications using passive lenses.

NEMA Performance Evaluation of CareMiBrain dedicated brain PET and Comparison with the whole-body and dedicated brain PET systems.

This article presents system performance studies of the CareMiBrain dedicated brain PET according to NEMA NU 2-2012 (for whole-body PETs) and NU 4-2008 (for preclinical PETs). This scanner is based on monolithic LYSO crystals coupled to silicon photomultipliers. The results obtained for both protocols are compared with current commercial whole body PETs and dedicated brain PETs found in the literature. Spatial resolution, sensitivity, NECR and scatter-fraction are characterized with NEMA standards, as well as an image quality study. A customized image quality phantom is proposed as NEMA phantoms do not fulfil the necessities of dedicated brain PETs. The full-width half maximum of the radial/tangential/axial spatial resolution of CareMiBrain reconstructed with FBP at 10 and 100 mm from the system center were, respectively, 1.87/1.68/1.39 mm and 1.86/1.91/1.40 mm (NU 2-2012) and 1.58/1.45/1.40 mm and 1.64/1.66/1.44 mm (NU 4-2008). Peak NECR was 49 kcps@287 MBq with a scatter fraction of 48% using NU 2-2012 phantom. The sensitivity was 13.82 cps/kBq at the center of the FOV (NU 2-2012) and 10% (NU 4-2008). Contrast recovery coefficients for customizing image quality phantom were 0.73/0.78/1.14/1.01 for the 4.5/6/9/12 mm diameter rods. The performance characteristics of CareMiBrain are at the top of the current technologies for PET systems. Dedicated brain PET systems significantly improve spatial resolution and sensitivity, but present worse results in count rate measurements and scatter-fraction tests. As for the comparison of preclinical and clinical standards, the results obtained for solid and liquid sources were similar.

Feasibility Study of a Small Animal PET Insert Based on a Single LYSO Monolithic Tube.

There are drawbacks with using a Positron Emission Tomography (PET) scanner design employing the traditional arrangement of multiple detectors in an array format. Typically PET systems are constructed with many regular gaps between the detector modules in a ring or box configuration, with additional axial gaps between the rings. Although this has been significantly reduced with the use of the compact high granularity SiPM photodetector technology, such a scanner design leads to a decrease in the number of annihilation photons that are detected causing lower scanner sensitivity. Moreover, the ability to precisely determine the line of response (LOR) along which the positron annihilated is diminished closer to the detector edges because the spatial resolution there is degraded due to edge effects. This happens for both monolithic based designs, caused by the truncation of the scintillation light distribution, but also for detector blocks that use crystal arrays with a number of elements that are larger than the number of photosensors and, therefore, make use of the light sharing principle. In this report we present a design for a small-animal PET scanner based on a single monolithic annulus-like scintillator that can be used as a PET insert in high-field Magnetic Resonance systems. We provide real data showing the performance improvement when edge-less modules are used. We also describe the specific proposed design for a rodent scanner that employs facetted outside faces in a single LYSO tube. In a further step, in order to support and prove the proposed edgeless geometry, simulations of that scanner have been performed and lately reconstructed showing the advantages of the design.

The MINDVIEW project: First results.

We present the first results of the MINDVIEW project. An innovative imaging system for the human brain examination, allowing simultaneous acquisition of PET/MRI images, has been designed and constructed. It consists of a high sensitivity and high resolution PET scanner integrated in a novel, head-dedicated, radio frequency coil for a 3T MRI scanner. Preliminary measurements from the PET scanner show sensitivity 3 times higher than state-of-the-art PET systems that will allow safe repeated studies on the same patient. The achieved spatial resolution, close to 1 mm, will enable differentiation of relevant brain structures for schizophrenia. A cost-effective and simple method of radiopharmaceutical production from 11C-carbon monoxide and a mini-clean room has been demonstrated. It has been shown that 11C-raclopride has higher binding potential in a new VAAT null mutant mouse model of schizophrenia compared to wild type control animals. A significant reduction in TSPO binding has been found in gray matter in a small sample of drug-naïve, first episode psychosis patients, suggesting a reduced number or an altered function of immune cells in brain at early stage schizophrenia.

Interobserver variability in rectum contouring in high-dose-rate brachytherapy for prostate cancer: A multi-institutional prospective analysis.

PURPOSE: The aim of this study was to evaluate the interobserver variability (IOV) of rectum contouring, and its dosimetric consequences, for high-dose-rate brachytherapy in patients with prostate cancer across multiple institutions. METHODS AND MATERIALS: Five radiation oncologists contoured rectums in 10 patients on transperineal ultrasound image sets after establishing a delineation consensus. The D0.1cc, D1cc, and D2cc rectum volume parameters were determined. The mean, standard deviation, and range of each dose-volume histogram parameter were evaluated for each patient. The IOV was determined using the coefficient of variation, and the dosimetric impacts on the total dose were analyzed by estimating the biologically equivalent dose (EQD2α/ß = 3). RESULTS: The interobserver coefficients of variation (±standard deviation) for the reported D0.1cc, D1cc, and D2cc were 5 ± 1.84%, 4 ± 1.26%, and 4 ± 1.33%, respectively. As for the impact on the total dose, the mean dose differences for D0.1cc, D1cc, and D2cc were 10 Gy, 7.3 Gy, and 6.6 Gy, respectively. CONCLUSIONS: The D2cc is robust as evident by the low IOV (<5%). However, some variability ranges almost overlap with the clinical threshold level, which may present dosimetric and clinical complications. General rectal contouring guidelines for prostate high-dose-rate brachytherapy are desirable to reduce discrepancies in delineation.

High-dose-rate brachytherapy boost for prostate cancer: Analysis of dose-volume histogram parameters for predicting late rectal toxicity.

PURPOSE: To determine the significance of dose-volume histogram parameters for predicting late rectal toxicity (LRT) after single-fraction high-dose-rate brachytherapy (HDRBT) boost and external beam radiotherapy (EBRT) in prostate cancer. MATERIALS AND METHODS: Three hundred patients with intermediate- or high-risk prostate cancer were included between August 2010 and March 2015. Treatment comprised a single-fraction HDRBT boost of 15.0 Gy plus EBRT (46.0 Gy delivered in 23 fractions) or an HDRBT boost of 9.5 Gy plus EBRT (60.0 Gy delivered in 30 fractions) if the seminal vesicles were infiltrated using real-time transrectal ultrasound-based planning. LRT was evaluated every 3 months after the end of the combined treatment using the Common Terminology Criteria for Adverse Events, version 4.0. The minimum dose received by the most exposed 0.1 and 2.0 cm3 volume of the rectum (D0.1 cc/D2cc) was analyzed by estimating the biologically equivalent rectal dose according to the recommendations of the Groupe Européen de Curiethérapie/European Society for Radiotherapy and Oncology and an ordinal regression analysis was performed. RESULTS: LRT was observed in 62 patients (20.7%) at a median followup of 33 (range, 2-68) months. Twenty patients (6.7%) developed grade 2 and 3 patients (1%) developed grade 3 LRT. A significant association was observed between D2cc and the probability of developing grade 1-3 LRT (p = 0.04). CONCLUSIONS: D2cc is associated with the occurrence of LRT in HDRBT-treated prostate cancer patients. The dose constraints proposed and recommended by experienced HDRBT centers must be investigated to determine the threshold dose through long-term and prospective studies.