Concept Development of an On-Chip PET System.

Organs-on-Chips (OOCs), microdevices mimicking in vivo organs, find growing applications in disease modeling and drug discovery. With the increasing number of uses comes a strong demand for imaging capabilities of OOCs. Positron Emission Tomography (PET) would be ideal for OOC imaging, however, current PET systems have insufficient spatial resolution for this task. In this work, we propose the concept of an On-Chip PET system capable of imaging OOCs. Our system consists of four detectors arranged around the OOC device. Each detector is made of two monolithic Lutetium-yttrium oxyorthosilicate (LYSO) crystals and covered with Silicon photomultipliers (SiPMs) on multiple surfaces. We use a Convolutional Neural Network (CNN) trained with data from a Monte Carlo Simulation (MCS) to predict the first gamma-ray interaction position inside the detector from the light patterns that are recorded by the SiPMs on the detector's surfaces. With the Line of Responses (LORs) created by the predicted interaction positions, we reconstruct with Simultaneous Algebraic Reconstruction Technique (SART). The CNN achieves a mean average prediction error of 0.78 mm in the best configuration. We use the trained network to reconstruct an image of a grid of 21 point sources spread across the field-of-view and obtain a mean spatial resolution of 0.53 mm. We demonstrate that it is possible to achieve a spatial resolution of almost 0.5 mm in a PET system made of multiple monolithic LYSO crystals by directly predicting the scintillation position from light patterns created with SiPMs. We observe that CNNs from the ResNet family perform better than those from the EfficientNet family and that certain surfaces encode significantly more information for the scintillation-point prediction than others.

Highly luminescent scintillating hetero-ligand MOF nanocrystals with engineered Stokes shift for photonic applications.

Large Stokes shift fast emitters show a negligible reabsorption of their luminescence, a feature highly desirable for several applications such as fluorescence imaging, solar-light managing, and fabricating sensitive scintillating detectors for medical imaging and high-rate high-energy physics experiments. Here we obtain high efficiency luminescence with significant Stokes shift by exploiting fluorescent conjugated acene building blocks arranged in nanocrystals. Two ligands of equal molecular length and connectivity, yet complementary electronic properties, are co-assembled by zirconium oxy-hydroxy clusters, generating crystalline hetero-ligand metal-organic framework (MOF) nanocrystals. The diffusion of singlet excitons within the MOF and the matching of ligands absorption and emission properties enables an ultrafast activation of the low energy emission in the 100 ps time scale. The hybrid nanocrystals show a fluorescence quantum efficiency of ~60% and a Stokes shift as large as 750 meV (~6000 cm-1), which suppresses the emission reabsorption also in bulk devices. The fabricated prototypal nanocomposite fast scintillator shows benchmark performances which compete with those of some inorganic and organic commercial systems.

Deep Learning for Predicting Gamma-Ray Interaction Positions in LYSO Detector.

Positron Emission Tomography (PET) is among the most commonly used medical imaging modalities in clinical practice, especially for oncological applications. In contrast to conventional imaging modalities like X-ray Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), PET retrieves in vivo information about biochemical processes rather than just anatomical structures. However, physical limitations and detector constraints lead to an order of magnitude lower spatial resolution in PET images. In recent years, the use of monolithic detector crystals has been investigated to overcome some of the factors limiting spatial resolution. The key to increasing PET systems' resolution is to estimate the gamma-ray interaction position in the detector as precisely as possible.In this work, we evaluate a Convolutional Neural Network (CNN) based reconstruction algorithm that predicts the gamma-ray interaction position using light patterns recorded with Silicon photomultipliers (SiPMs) on the crystal's surfaces. The algorithm is trained on data from a Monte Carlo Simulation (MCS) that models a gamma point source and a detector consisting of Lutetium-yttrium oxyorthosilicate (LYSO) crystals and SiPMs added to five surfaces. The final Mean Absolute Error (MAE) on the test dataset is 1.48 mm.

Vacuum ultraviolet silicon photomultipliers applied to BaF2cross-luminescence detection for high-rate ultrafast timing applications.

Inorganic scintillators are widely used for fast timing applications in high-energy physics (HEP) experiments, time-of-flight positron emission tomography and time tagging of soft and hard x-ray photons at advanced light sources. As the best coincidence time resolution (CTR) achievable is proportional to the square root of the scintillation decay time it is worth studying fast cross-luminescence, for example in BaF2which has an intrinsic yield of about 1400 photons/MeV. However, emission bands in BaF2are located in the deep-UV at 195 nm and 220 nm, which sets severe constraints on photodetector selection. Recent developments in dark matter and neutrinoless double beta decay searches have led to silicon photomultipliers (SiPMs) with photon detection efficiencies of 20%-25% at wavelengths of 200 nm. We tested state-of-the-art devices from Fondazione Bruno Kessler and measured a best CTR of 51 ± 5 ps full width at half maximum when coupling 2 mm × 2 mm × 3 mm BaF2crystals excited by 511 keV electron-positron annihilation gammas. Using these vacuum ultraviolet SiPMs we recorded the scintillation kinetics of samples from Epic Crystal under 511 keV excitation, confirming a fast decay time of 855 ps with 12.2% relative light yield and 805 ns with 84.0% abundance, together with a smaller rise time of 4 ps beyond the resolution of our setup. The total intrinsic light yield was determined to be 8500 photons/MeV. We also revealed a faster component with 136 ps decay time and 3.7% light yield contribution, which is extremely interesting for the fastest timing applications. Timing characteristics and CTR results on BaF2samples from different producers and with different dopants (yttrium, cadmium and lanthanum) are given, and clearly show that the the slow 800 ns emission can be effectively suppressed. Such results ultimately pave the way for high-rate ultrafast timing applications in medical diagnosis, range monitoring in proton or heavy ion therapy and HEP.

Time-of-flight computed tomography - proof of principle.

Computed tomography has greatly improved over the last decade, especially through x-ray dose exposure reduction while maintaining image quality. Herein, a new concept is proposed to improve the contrast-to-noise ratio (CNR) by including the time-of-flight (TOF) information of individual photons to obtain further insight on the photon's trajectory and to reject scatter contribution. The proof of the concept relies on both simulation and experimental measurements in a cone-beam computed tomography arrangement. Results show a statistical difference between the TOF of scattered and primary photons exploitable in TOF computed tomography. For a large volume of the size of a human abdomen, a scatter reduction from 296% to 4% is achieved in our simulation setup with perfect timing measurements which yields a 110% better CNR, or a dose reduction by a factor of four. Cup artifacts are also reduced from 24.7% to 0.8%, and attenuation inaccuracies are improved from -26.3% to -0.8%. With 100 ps and 10 ps FWHM timing jitters, respectively 75% and 95% of the scatter contribution can be removed with marginal gains below 10 ps. Experimental measurements confirm the feasibility of measuring statistical differences between the TOF of scattered and primary photons.

On light sharing TOF-PET modules with depth of interaction and 157 ps FWHM coincidence time resolution.

The performance of a light sharing and recirculation mechanism that allows the extraction of depth of interaction (DOI) are investigated in this paper, with a particular focus on timing. In parallel, a method to optimize the coincidence time resolution (CTR) of PET detectors by use of the DOI information is proposed and tested. For these purposes, a dedicated 64-channels readout setup has been developed with intrinsic timing resolution of 16 ps FWHM. Several PET modules have been produced, based on LYSO:Ce scintillators and commercial silicon photomultiplier (SiPM) arrays, with [Formula: see text] mm2 individual SiPM size. The results show the possibility to achieve a timing resolution of 157 ps FWHM, combined with the already demonstrated spatial resolution of 1.5 mm FWHM, DOI resolution of 3 mm FWHM, and energy resolution of 9% FWHM at 511 keV, with 15 mm long crystals of section [Formula: see text] mm2 and [Formula: see text] mm2. At the same time, the extraction of the DOI coordinate has been demonstrated not to deteriorate the timing performance of the PET module.

Towards a metamaterial approach for fast timing in PET: experimental proof-of-concept.

Achieving fast timing in positron emission tomography (PET) at the level of few tens of picoseconds of picoseconds is limited by the photon emission rate of existent materials with standard scintillation mechanisms. This has led to consider quantum confined excitonic sub-1 ns emission in semiconductors as a viable solution to enhance the amount of fast-emitted photons produced per gamma event. However the introduction of nanocrystals and nanostructures into the domain of radiation detectors is a challenging problem. In order to move forward along this line, the standard bulk detector geometry and readout should be updated to allow for the implementation of new materials and within others, compensate for some of their intrinsic limitations. In this paper we will cover two study cases in which a fast emitter is combined with state-of-the-art scintillators in a sampling geometry designed to provide better timing for a fraction of the 511 keV events. For this test, we use a fast plastic scintillator BC-422 able to deliver a detector time resolution (DTR) of 25 ps FWHM (equivalent coincidence time resolution CTR of 35 ps) and we combined it with LYSO or BGO 200 [Formula: see text]m thick plates building a sampling pixel composed by two active scintillating materials. We develop a new proof of concept readout that allows for the identification of different types of events, carrying standard or improved timing information. Results are showing a DTR of 67 ps FWHM (equivalent to a CTR of 95 ps) for one third of the events depositing 511 keV in the BGO + BC-422 [Formula: see text] mm3 sampling pixel. The other two third of the 511 keV events perform like standard bulk 3 mm long BGO crystals with a time resolution of around 117 ps (equivalent to a CTR of 165 ps). For the case of LYSO + BC-422 sampling pixel, shared 511 keV events reach a DTR of 39 ps (CTR of 55 ps) in comparison to 57 ps (CTR of 83 ps) for 511 keV events fully contained in LYSO of the same size. This work is a step forward in the integration of fast semiconductor nanocrystals and nanostructures with present detector technologies.

A new method for depth of interaction determination in PET detectors.

A new method for obtaining depth of interaction (DOI) information in PET detectors is presented in this study, based on sharing and redirection of scintillation light among multiple detectors, together with attenuation of light over the length of the crystals. The aim is to obtain continuous DOI encoding with single side readout, and at the same time without the need for one-to-one coupling between scintillators and detectors, allowing the development of a PET scanner with good spatial, energy and timing resolutions while keeping the complexity of the system low. A prototype module has been produced and characterized to test the proposed method, coupling a LYSO scintillator matrix to a commercial SiPMs array. Excellent crystal separation is obtained for all the scintillators in the array, light loss due to depolishing is found to be negligible, energy resolution is shown to be on average 12.7% FWHM. The mean DOI resolution achieved is 4.1 mm FWHM on a 15 mm long crystal and preliminary coincidence time resolution was estimated in 353 ps FWHM.

Longitudinal study of blood pressure and white matter hyperintensities: the EVA MRI Cohort.

OBJECTIVE: To investigate the relationship between baseline hypertension and severity of white matter hyperintensities (WMH) at 4-year follow-up in a sample of subjects aged 59 to 71 years old at entry. METHODS: Subjects were participants in the Epidemiology of Vascular Ageing study, a longitudinal study on vascular aging and cognitive decline. At 4-year follow-up, 845 subjects had a cerebral MRI. MRI examinations were read by a single rater to determine the severity of WMH, ranging from absent to severe. Hypertension at each wave of the study was defined as systolic blood pressure > or =160 mm Hg, diastolic blood pressure > or =95 mm Hg, or use of antihypertensive medication. RESULTS: Hypertension at baseline was significantly associated with an increased risk of having severe WMH at 4-year follow-up. When taking into account both blood pressure levels and antihypertensive drug intake, analysis showed that the risk of having severe WMH was significantly reduced in subjects with normal blood pressure taking antihypertensive medication compared with those with high blood pressure taking antihypertensive agents. Cross-sectional relationships between hypertension and WMH at 4-year follow-up showed that the frequency of severe WMH was significantly higher in people who were hypertensive at both baseline and 4-year follow-up than those who were hypertensive only at 4-year follow-up. CONCLUSIONS: Hypertension is a major risk factor for severe WMH. Subjects taking antihypertensive drugs and who have controlled blood pressure had a reduced risk of severe WMH. Longitudinal studies are needed to investigate whether reduction of the development of WMH, by treatment and prevention of hypertension, might reduce the subsequent risk of cognitive deterioration or stroke.

[Leptomeningeal gliomatosis. 2 clinicopathological cases]. / Gliomatose leptoméningée. Deux cas clinico-pathologiques.

Leptomeningeal gliomatosis is a diffuse glial infiltration of the subarachnoid space. It is primary and very rare when primary astrocytoma arises in the leptomeninges from heterotopic neuroglial tissue; it is secondary and more frequently reported when associated with a medullar or cerebral intraparenchymal astrocytoma and secondary involvement of the leptomeninges. Primary and secondary forms are difficult to differentiate before neuropathological examination. The authors report 2 anatomo-clinical cases of leptomeningeal gliomatosis in adults, with clinical courses of 6 months and 40 days respectively. The initial clinical picture was aseptic chronic or subacute meningitis. Cytologic examinations of the cerebrospinal fluid (CSF) showed moderate lymphocytosis, with elevated protein and low glucose levels, without abnormal cells. On case 2 CT scan and in case 1 spinal MRI isolated diffuse meningeal contrast enhancement was present, without intraparenchymal lesion. The neuropathological study revealed a diffuse astrocytoma glial leptomeningeal tumour with a focal involvement of the central nervous system (spinal cord in one case, temporal lobe in the other). In conclusion, an isolated aseptic lymphocytosis meningitis with meningeal abnormal signal may reveal leptomeningeal gliomatosis. Neuropathological examination can distinguish primary from secondary forms.

Contribution of MR-angiography to the diagnosis and the therapeutic indication and follow-up of intracranial aneurysms.

The purpose of this study was to evaluate MR-Angiography (MRA) in comparison with digital angiography in the diagnosis, therapeutic indication and therapeutic follow-up of cerebral aneurysms. Out of 27 patients explored by angiography and MRA, 17 had aneurysm, 5 had an aneurysm excluded by a detachable balloon, and 5 without aneurysm were used as controls. MRA, performed by the paradoxical enhancement technique, required a 3 DFT acquisition with short TR and TE (40-8 ms) in gradient echo, with a 15 degrees flip angle. Analysis of angiograms and partitions was compared with that of angiography. Sixteen of the 17 aneurysms were found by a study of both angiograms and partitions. The result was doubtful in 1 patient. No false-negative result was recorded. Spasm was always detected, but the neck of the aneurysm was never sufficiently well defined. The quality of angiogram depends on the type of balloon used in the patients treated: only the balloon without metallic index did not induce an artefact. Thus, MRA seems to be useful in the detection of cerebral aneurysms, and the absence of artefact induced by detachable balloons without metallic index could allow a therapeutic follow-up. But for the moment, arteriography remains the reference for pretherapeutic evaluation.

Lhermitte-duclos disease. A rare cause of intracranial hypertension in adults.

In a 39-year old woman hospitalized for intracranial hypertension MRI revealed the presence of abnormal areas in the cerebellar cortex. The negative results of investigations for possible causes, as well as the appearance of radiological abnormalities and their persistence over a 6-month period incited the authors to make a tentative diagnosis of Lhermitte-Duclos disease, despite the lack of anatomicopathological evidence.

[Radio-anatomy of the infratemporal fossa. Pterygo-maxillary region]. / Radio-anatomie de la fosse infra-temporale. Région ptérygo-maxillaire.

The modern imaging techniques (computed tomography, MRI), allow a new approach of the limits and contents of the infratemporal fossa. This better anatomical knowledge allows distinguishing three distinct subregions, hence providing better interdisciplinary understanding.